Updated on 2021/12/13

写真a

 
YOSHINO Tadashi
 
Organization
Medicine, Dentistry and Pharmaceutical Sciences Professor
Position
Professor
Profile
リンパ腫関連疾患の診断、研究を行っています。ファイルしている症例数は、25000件を超えています。
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Degree

  • 医学博士

Research Interests

  • 人体病理

  • 血液病理

  • リンパ腫

  • HematopathologyMalignant lymphoma

  • Human Pathology

Research Areas

  • Life Science / Experimental pathology

  • Life Science / Human pathology

Education

  • Okayama University    

    - 1985

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  • Okayama University   医学研究科   病理学

    - 1985

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    Country: Japan

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  • Okayama University    

    - 1981

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  • Okayama University   医学部   医学科

    - 1981

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    Country: Japan

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Research History

  • 岡山大学 副学長

    2014 - 2017

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  • Okayama University

    2011 - 2015

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  • 岡山大学医歯薬学総合研究科 教授

    2004 - 2021

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  • 米国スタンフォード大学 病理学教室 研究員

    1990 - 1992

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Professional Memberships

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Committee Memberships

  • 日本病理学会   学術委員  

    2020.4 - 2022.3   

  • 国際病理アカデミー日本支部   会長  

    2019   

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    Committee type:Academic society

    国際病理アカデミー日本支部

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  • 日本病理学会   監事  

    2018 - 2020   

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  • 日本リンパ網内系学会   理事長  

    2018 - 2020   

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    Committee type:Academic society

    日本リンパ網内系学会

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  • 国際リンパ腫研究グループ(ILSG)   メンバー  

    2013   

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    Committee type:Academic society

    国際リンパ腫研究グループ(ILSG)

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  • 日本リンパ網内系学会   常任理事  

    2012 - 2016   

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    Committee type:Academic society

    日本リンパ網内系学会

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  • 日本病理学会   支部学術委員会委員長  

    2012 - 2013   

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  • 日本病理学会中国四国支部   支部長  

    2010 - 2014   

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    Committee type:Academic society

    日本病理学会中国四国支部

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  • 日本病理学会   理事  

    2010 - 2013   

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    Committee type:Academic society

    日本病理学会

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  • Japanese Society of Pathology   Director  

    2010 - 2013   

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    Committee type:Academic society

    Japanese Society of Pathology

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  • 国際病理アカデミー日本支部   IAP奨励賞選考委員長  

    2010   

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    Committee type:Academic society

    国際病理アカデミー日本支部

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  • 日本癌学会   評議員  

    2008   

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    Committee type:Academic society

    日本癌学会

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  • 日本リンパ網内系学会   理事  

    2008 - 2011   

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    Committee type:Academic society

    日本リンパ網内系学会

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  • 国際病理アカデミー日本支部   理事  

    2007 - 2012   

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    Committee type:Academic society

    国際病理アカデミー日本支部

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  • 国際病理アカデミー日本支部   理事  

    2007 - 2011   

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    Committee type:Academic society

    国際病理アカデミー日本支部

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  • 国際病理アカデミー   日本支部理事  

    2007   

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    Committee type:Academic society

    国際病理アカデミー

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  • 日本リンパ網内系学会   理事  

    2007   

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    Committee type:Academic society

    日本リンパ網内系学会

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  • 日本がん学会   評議員  

    2007   

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    Committee type:Academic society

    日本がん学会

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  • 日本胃癌学会   評議員  

    2006 - 2008   

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    Committee type:Academic society

    日本胃癌学会

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  • 日本臨床細胞学会岡山県支部   支部長  

    2006   

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    Committee type:Academic society

    日本臨床細胞学会岡山県支部

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  • 日本病理学会   日本病理学会病理専門医審査委員会委員  

    2004 - 2005   

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    Committee type:Academic society

    日本病理学会

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  •   - 日本リンパ網内系学会 学術委員会委員長(2012-)  

    1981   

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Papers

  • PD-L1 expression is associated with the spontaneous regression of patients with methotrexate-associated lymphoproliferative disorders. International journal

    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   2021.11

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    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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  • Transformed diffuse large B-cell lymphoma from marginal zone lymphoma in the anterior mediastinum: A case report and review of the literature.

    Wataru Kitamura, Noboru Asada, Tetsuya Tabata, Rei Shibata, Tatsuya Nishi, Yuka Kato, Hiroki Takasuka, Hideaki Fujiwara, Daisuke Ennishi, Hisakazu Nishimori, Nobuharu Fujii, Ken-Ichi Matsuoka, Katsuyuki Kiura, Tadashi Yoshino, Yoshinobu Maeda

    Journal of clinical and experimental hematopathology : JCEH   2021.11

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    Marginal zone lymphoma (MZL) arising from the anterior mediastinum is rare. In the majority of reported cases, the tumor was incidentally discovered, reflecting its indolent clinical features. We present a 38-year-old woman who had no medical history, and presented with a bulky anterior mediastinal tumor complicated by life-threatening compression of the vasculature and bronchi. Biopsy specimens of the neoplasm suggested transformed diffuse large B-cell lymphoma (DLBCL) from MZL. To our best knowledge, this is the first case report of anterior mediastinum MZL associated with an aggressive clinical course and life-threatening complications likely due to transformation to DLBCL.

    DOI: 10.3960/jslrt.21010

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  • Primary Gastrointestinal T-Cell Lymphoma and Indolent Lymphoproliferative Disorders: Practical Diagnostic and Treatment Approaches. International journal

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

    Cancers   13 ( 22 )   2021.11

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    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?

    DOI: 10.3390/cancers13225774

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  • Involvement of multiple scavenger receptors in advanced glycation end product-induced vessel tube formation in endothelial cells. International journal

    Yui Yamazaki, Hidenori Wake, Takashi Nishinaka, Omer Faruk Hatipoglu, Keyue Liu, Masahiro Watanabe, Takao Toyomura, Shuji Mori, Tadashi Yoshino, Masahiro Nishibori, Hideo Takahashi

    Experimental cell research   408 ( 1 )   112857 - 112857   2021.11

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    Toxic advanced glycation end products (toxic AGEs) derived from glycolaldehyde (AGE3) have been implicated in the development of diabetic vascular complications such as retinopathy characterised by excessive angiogenesis. Different receptor types, such as receptor for AGEs (RAGE), Toll like receptor-4 and scavenger receptors, are expressed in endothelial cells and contribute to AGE-elicited alteration of cell function. In the present study, we examined the involvement of AGE-related receptors on AGE-induced angiogenesis in endothelial cells. The effects of pharmacological inhibitors or receptor neutralizing antibodies on AGE3-induced tube formation were investigated using the in vitro Matrigel tube formation assay in b.End5 cells (mouse endothelial cells). AGE3-induced signalling pathways and receptor expression changes were analysed by Western blot analysis and flow cytometry, respectively. Both FPS-ZM1, a RAGE inhibitor, and fucoidan, a ligand for scavenger receptors, suppressed AGE3-induced tube formation. Cocktails of neutralizing antibodies against the scavenger receptors CD36, CD163 and LOX-1 prevented AGE3-induced tube formation. AGE3 activated mTOR signalling, resulting in facilitation of tube formation. Activation of the AGE-RAGE pathway also led to the upregulation of scavenger receptors. Taken together, our findings suggest that the scavenger receptors CD36, CD163 and LOX-1 in conjunction with the RAGE receptor work together to mediate toxic AGE-induced facilitation of angiogenesis.

    DOI: 10.1016/j.yexcr.2021.112857

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

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

    Diagnostics (Basel, Switzerland)   11 ( 11 )   2021.10

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    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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  • 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.

    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   2021.9

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    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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  • 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. International journal

    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   2021.8

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  • Sarcoidosis-lymphoma syndrome with portal hypertension: diagnostic clues and approach. International journal

    Fumio Chikamori, Kenji Yorita, Tadashi Yoshino, Satoshi Ito, Miki Mizobuchi, Koji Ueta, Kai Mizobuchi, Shigeto Shimizu, Kazumasa Nanjo, Sawaka Yukishige, Jun Iwabu, Hisashi Matsuoka, Norihiro Hokimoto, Hiromichi Yamai, Kazuhisa Onishi, Nobuyuki Tanida, Niranjan Sharma

    Radiology case reports   16 ( 8 )   2192 - 2201   2021.8

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    Sarcoidosis-lymphoma syndrome associated with portal hypertension is very rare. A 68-year-old female presented with a 5 kg weight loss in 6 months. Soluble interleukin-2 receptor activity was increased and total platelet count was decreased. Contrast-enhanced computed tomography showed the presence of hepatosplenomegaly and a 3 cm-sized tumor in segment 3 of the liver. The hepatic venous catheterization showed mild portal hypertension. On fluorodeoxyglucose-positron emission tomography/computed tomography, progressive malignant lymphoma was suspected. However, bone marrow biopsy showed multiple noncaseating granulomas. A laparoscopic liver biopsy revealed that the liver tumor had features of Hodgkin lymphoma. There were multiple noncaseating epithelioid granulomas in the portal tracts of the liver. Splenectomy for splenomegaly and partial hepatectomy for the liver tumor were performed. Pathological examination of the resected specimens revealed multiple noncaseating epithelioid granulomas in the liver and spleen. Histopathology of the liver tumor confirmed classic Hodgkin lymphoma with mixed cellularity. We conclude that hepatic venous catheterization, positron emission tomography/computed tomography, and pathological examinations of bone marrow, liver, and spleen are crucial for the diagnosis of sarcoidosis-lymphoma syndrome associated with portal hypertension.

    DOI: 10.1016/j.radcr.2021.05.045

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  • Secretory carcinoma of the skin with lymph node metastases and recurrence in both lungs: A case report. International journal

    Kohei Taniguchi, Hiroyuki Yanai, Tatsuya Kaji, Toshio Kubo, Daisuke Ennishi, Akira Hirasawa, Tadashi Yoshino

    Journal of cutaneous pathology   48 ( 8 )   1069 - 1074   2021.8

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    Secretory carcinoma of the skin is an extremely rare adnexal tumor, histopathologically identical to homologous lesions in the salivary glands and breast tissue. Although this tumor was previously reported as indolent, we report a case of secretory carcinoma of the skin with metastases and recurrence. The patient, a 31-year-old women, had a subcutaneous mass in the right axilla. The resected specimen contained a circumscribed mass, with proliferating tumor cells that exhibited prominent nucleoli. They exhibited glandular and papillary growth patterns and there were amphophilic secretions in the glands. Immunohistochemically, the tumor cells were positive for mammaglobin and S100. The tumor was surrounded by sweat glands and there was no mammary glandular tissue, suggesting that it was derived from axillary sweat glands. Accordingly, we made a diagnosis of secretory carcinoma of the skin. Four years after the operation, there were metastases in both lungs. The resected specimen revealed a tumor identical to that of the original skin tumor. Next-generation sequencing-based multiplex gene assay performed on the metastatic tissue revealed an ETV6-NTRK3 fusion gene. This is a rare case report of secretory carcinoma of the skin with lymph node metastases and recurrence in both lungs.

    DOI: 10.1111/cup.14028

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  • Multiple small tumor formation on both surfaces of the aortic valve cusps in Epstein-Barr virus-associated T/NK-cell lymphoproliferative disease: a case report.

    Ryuta Tai, Hiroyuki Irie, Yusuke Kinugasa, Hideki Teshima, Masahiko Ikebuchi, Keiko Kaneko, Nobuhiro Miyazaki, Hideaki Enzan, Tadashi Yoshino

    General thoracic and cardiovascular surgery   69 ( 6 )   1012 - 1015   2021.6

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    A 41-year-old woman presented acute cerebral infarction. Transesophageal echocardiography revealed multiple masses only on both surfaces of the aortic valve cusps. There was no primary lesion outside the heart according to various examinations. After treatment for cerebral infarction, we replaced the aortic valve instead of preservation because the intraoperative histological examination reported that malignancy was highly suspected. Contrary to the rapid frozen section diagnosis, histological and immunohistochemical examinations failed to exhibit malignancy. The tumors were composed of atypical large lymphoid cells and they were assessed to be related to T-/natural killer-cells. Furthermore, Epstein-Barr virus related markers were also positive. Her three-year postoperative course was uneventful without chemotherapy. We report an extremely rare case of Epstein-Barr virus-associated T-/natural killer-cell lymphoproliferative disease which formed multiple small tumors on both surfaces of the aortic valve.

    DOI: 10.1007/s11748-021-01613-5

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  • モガムリズマブ投与後に移植片対宿主病が重症化した成人T細胞白血病の3例

    横山 恵美, 赤松 由規, 山崎 修, 山本 晃, 大山 矩史, 神原 由依, 淺田 騰, 谷口 恒平, 吉野 正, 森実 真

    日本皮膚科学会雑誌   131 ( 5 )   1390 - 1390   2021.5

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    Language:Japanese   Publisher:(公社)日本皮膚科学会  

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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

    日本リンパ網内系学会会誌   61   101 - 101   2021.5

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    Language:Japanese   Publisher:(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

    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

    日本リンパ網内系学会会誌   61   122 - 122   2021.5

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

    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   2021.5

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    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.

    DOI: 10.1007/s00428-020-02967-6

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  • TdT-positive primary cutaneous diffuse large B-cell lymphoma, leg type phenotypically mimicking B-lymphoblastic lymphoma. International journal

    Mai Endo, Mikio Ohtsuka, Yukina Watanabe, Shohei Igari, Nobuyuki Kikuchi, Kohei Taniguchi, Tadashi Yoshino, Toshiyuki Yamamoto

    Journal of cutaneous pathology   48 ( 5 )   721 - 724   2021.5

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    DOI: 10.1111/cup.13955

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  • Diagnostic Utility of SOX4 Expression in Adult T-Cell Leukemia/Lymphoma. International journal

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

    Diagnostics (Basel, Switzerland)   11 ( 5 )   2021.4

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    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. International journal

    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 )   2021.4

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    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.

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  • Nodal Peripheral T-cell Lymphoma with T Follicular Helper Phenotype Presenting as Chorea during Treatment: A Case Report and Literature Review.

    Wataru Kitamura, Daisuke Ennishi, Ryoya Yukawa, Ryo Sasaki, Chikamasa Yoshida, Hiroki Takasuka, Hideaki Fujiwara, Noboru Asada, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Koji Abe, Tadashi Yoshino, Yoshinobu Maeda

    Internal medicine (Tokyo, Japan)   60 ( 19 )   3155 - 3160   2021.4

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    A 72-year-old man presented with chorea while undergoing treatment for recurrence of nodal peripheral T-cell lymphoma with T follicular helper (TFH) phenotype. An examination by brain N-isopropyl-p-iodoamphetamine (123I-IMP)-single photon emission computed tomography (SPECT) revealed no abnormalities other than a decreased cerebral blood flow (CBF) in the left striatum. After four courses of salvage chemotherapy, his clinical symptoms and asymmetric cerebral perfusion improved, suggesting that the decreased CBF had caused chorea. The significance of brain SPECT has not been fully clarified in patients with chorea-associated malignant lymphoma, warranting further investigations. Brain SPECT is an alternative approach to identify abnormalities in such patients.

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  • DNA mismatch repair deficiency and p53 abnormality are age-related events in mixed endometrial carcinoma with a clear cell component. International journal

    Naoyuki Ida, Keiichiro Nakamura, Masayuki Saijo, Atsuko Nasu, Tadashi Yoshino, Hisashi Masuyama, Hiroyuki Yanai

    Pathology, research and practice   220   153383 - 153383   2021.4

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    Mixed endometrial carcinoma (MEC) is defined as a tumor composed of two or more spatially distinct subtypes, at least one of which is serous or clear cell carcinoma. In this study, the clinicopathological features of 15 MEC cases containing a clear cell component (MEC-C) were investigated. The ages of patients ranged from 32 to 83 years (median, 61 years). The combinations of carcinoma components observed were endometrioid and clear cell in ten patients; endometrioid, clear cell and serous in three; and clear cell and serous in two. Immunohistochemically, nine had DNA mismatch repair (MMR) protein deficiency (MMR-d), nine had loss of ARID1A and three cases had aberrant p53 expression. MMR-d and loss of ARID1A showed a strong correlation. Only one case showed both MMR-d and aberrant p53 expression. The patients with MMR-d were younger than those without MMR-d (median; 58 years vs. 71 years). Loss of ARID1A also showed significant predilection for younger women than ARID1A intact cases. In conclusion, MMR-d was observed in 60 % of MEC-C, showed predilection for young women, and was associated with ARID1A loss. In contrast, non- MMR-d MEC-C occurred in elder women and some tumors may associate with TP53 mutation. These findings suggest that MEC-C develop via two different molecular mechanisms and they are age-related events.

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  • Correction to: PD-L1 expression in tongue squamous cell carcinoma (Medical Molecular Morphology, (2021), 54, 1, (52-59), 10.1007/s00795-020-00261-7)

    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   2021.3

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    In the original publication of the article an affiliation should be added to the first author “Naoki Akisada” as given below:5Departments of Otolaryngology Head and Neck Surgery,Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences, Okayama 700‑8558,Japan

    DOI: 10.1007/s00795-020-00270-6

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  • A randomized phase 2/3 study of R-CHOP vs CHOP combined with dose-dense rituximab for DLBCL: the JCOG0601 trial. International journal

    Ken Ohmachi, Tomohiro Kinoshita, Kensei Tobinai, Gakuto Ogawa, Tomonori Mizutani, Nobuhiko Yamauchi, Noriko Fukuhara, Toshiki Uchida, Kazuhito Yamamoto, Kana Miyazaki, Norifumi Tsukamoto, Shinsuke Iida, Takahiko Utsumi, Isao Yoshida, Yoshitaka Imaizumi, Takashi Tokunaga, Shinichiro Yoshida, Yasufumi Masaki, Tohru Murayama, Yoshihiro Yakushijin, Youko Suehiro, Kisato Nosaka, Nobuaki Dobashi, Junya Kuroda, Yasushi Takamatsu, Dai Maruyama, Kiyoshi Ando, Kenichi Ishizawa, Michinori Ogura, Tadashi Yoshino, Tomomitsu Hotta, Kunihiro Tsukasaki, Hirokazu Nagai

    Blood advances   5 ( 4 )   984 - 993   2021.2

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    Rituximab plus cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) is the standard of care for untreated diffuse large B-cell lymphoma (DLBCL). However, the schedule for rituximab administration has not been optimized. To compare standard R-CHOP with CHOP plus dose-dense weekly rituximab (RW-CHOP) in patients with untreated DLBCL, we conducted a phase 2/3 study (JCOG0601, jRCTs031180139). Patients were randomly assigned to R-CHOP (CHOP-21 with 8 doses of rituximab once every 3 weeks [375 mg/m2]) or RW-CHOP (CHOP-21 with 8 doses of weekly rituximab [375 mg/m2]) groups. The primary end point of the phase 2 component was percent complete response (%CR) of the RW-CHOP arm, whereas that of the phase 3 component was progression-free survival (PFS). Between December 2007 and December 2014, 421 untreated patients were randomly assigned to R-CHOP (213 patients) or RW-CHOP (208 patients). The %CR in the RW-CHOP arm was 85.3% and therefore met the prespecified decision criteria for the phase 2 component. With a median follow-up of 63.4 months, the 3-year PFS and overall survival were 79.2% and 88.7% in the R-CHOP arm and 80.3% and 90.4% in the RW-CHOP arm, respectively. There was no significant difference in PFS (hazard ratio, 0.95; 90.6% confidence interval, 0.68-1.31). Although the safety profile and efficacy of RW-CHOP was comparable with R-CHOP and its tolerability was acceptable, weekly rituximab in combination with CHOP during the early treatment period did not improve PFS in untreated patients with DLBCL. This trial was registered at jrct.niph.go.jp as #jRCTs031180139.

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  • Consolidation with 90 Yttrium-ibritumomab tiuxetan after bendamustine and rituximab for relapsed follicular lymphoma. International journal

    Katsuhiro Miura, Hideki Tsujimura, Yasufumi Masaki, Masaki Iino, Jun Takizawa, Yoshinobu Maeda, Kazuhiko Yamamoto, Shinobu Tamura, Akiyo Yoshida, Hideo Yagi, Isao Yoshida, Koichi Kitazume, Taro Masunari, Ilseung Choi, Yasutaka Kakinoki, Ritsuro Suzuki, Tadashi Yoshino, Shigeo Nakamura, Yoshihiro Hatta, Takashi Yoshida, Masatoshi Kanno

    Hematological oncology   39 ( 1 )   51 - 59   2021.2

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    Bendamustine and rituximab (BR) are widely used in patients with follicular lymphoma (FL) previously treated with conventional immunochemotherapy, but the role of consolidation radioimmunotherapy in these patients is unknown. This study evaluated the efficacy and safety of consolidation with 90 Yttrium-ibritumomab tiuxetan (90 Y-IT) after re-induction therapy with BR in patients with previously treated FL. This study included adult patients with relapsed FL who had undergone one or two prior therapies. Re-induction therapy with BR was administered every 4 weeks up to 4-6 cycles. If patients achieved at least partial response, 90 Y-IT was administered as consolidation therapy. The primary endpoint was 2-year progression-free survival (PFS) after consolidation. A total of 24 FL patients (median age 60 years) who had undergone one (n = 17) or two (n = 7) prior treatments received BR. After BR therapy, 22 patients proceeded to consolidation with 90 Y-IT, resulting in an overall 88% response rate to the protocol treatment. Within a median observation period of 46.8 months, the estimated 2-year PFS rate after the consolidation among the 22 patients receiving 90 Y-IT was 59% (95% confidence interval [CI], 38%-77%). Patients whose remission after previous treatment had lasted ≥2 years had a significantly higher 2-year PFS rate than patients whose remission after previous treatment had been <2 years (68% vs. 33%, Wilcoxon p = 0.0211). Major adverse events during the protocol treatment and within 2 years after the consolidation were hematological toxicities, but they were generally acceptable. Consequently, the estimated 2-year overall survival after the consolidation was 95% (95% CI, 74%-99%). In conclusion, in a subset of patients with previously treated FL, 90 Y-IT consolidation after BR re-induction conferred a durable remission, indicating that consolidation therapy using 90 Y-IT may be a novel therapeutic option for patients with relapsed FL (UMIN000008793).

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  • Epstein-Barr Virus-Positive Mucocutaneous Ulcer: A Unique and Curious Disease Entity. International journal

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

    International journal of molecular sciences   22 ( 3 )   2021.1

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    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.

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  • A Case of Myoepithelial Hamartoma: Morphological Variation Supported by OCT4 Expression. International journal

    Takehiro Tanaka, Kenji Nishida, Masaya Iwamuro, Satoru Kikuchi, Tadashi Yoshino

    Case reports in gastrointestinal medicine   2021   6617370 - 6617370   2021

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    In this report, we describe a patient with myoepithelial hamartoma, which is regarded as synonymous with adenomyosis and heterotopic pancreas. Endoscopy revealed a submucosal tumor in the antrum of the stomach. Subsequently, distal gastrectomy with Roux-en-Y reconstruction was performed. Histological findings of adenomyomatous lesion and heterotopic pancreatic tissue were observed in this lesion. The distribution of OCT4, which is a pluripotency marker, varied in each part.

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

    Tadashi Yoshino, Takehiro Tanaka, Yasuharu Sato

    Journal of clinical and experimental hematopathology : JCEH   60 ( 4 )   124 - 129   2020.12

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    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. International journal

    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 )   2020.12

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    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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  • Clinicopathological analysis of 34 Japanese patients with EBV-positive mucocutaneous ulcer. International journal

    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   2020.12

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    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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  • Deletion of BART miRNA-encoding cluster in Epstein-Barr virus DNA in classic Hodgkin lymphoma. International journal

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

    Pathology international   70 ( 12 )   1032 - 1033   2020.12

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  • Clinicopathological significance of CD79a expression in classic Hodgkin lymphoma.

    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   2020.9

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    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.

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

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

    Medical molecular morphology   53 ( 3 )   149 - 155   2020.9

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

    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   2020.8

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  • PD-L1 expression in tongue squamous cell carcinoma Reviewed

    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   2020.7

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

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

    Pathology international   70 ( 7 )   391 - 402   2020.7

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    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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  • 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   60   82 - 82   2020.7

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  • 濾胞性リンパ腫と診断後約1年で組織学的形質転換を来した難治性リンパ腫

    寺崎 靖, 米山 聖子, 齋藤 勝彦, 西村 碧フィリーズ, 田端 哲也, 吉野 正

    日本検査血液学会雑誌   21 ( 学術集会 )   S259 - S259   2020.6

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  • An Endoscopic Biopsy Specimen Contains Adequate Lymphocytes for Flow Cytometric Analysis of Light Chain Expression in the Gastrointestinal Mucosa. International journal

    Masaya Iwamuro, Katsunori Matsueda, Takahide Takahashi, Sizuma Omote, Takehiro Tanaka, Daisuke Ennishi, Fumio Otsuka, Tadashi Yoshino, Hiroyuki Okada

    Annals of clinical and laboratory science   50 ( 3 )   348 - 353   2020.5

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    OBJECTIVE: Flow cytometry has not been widely used in routine clinical practice for the diagnosis of gastrointestinal lymphoma; this is mainly because of the absence of an appropriate protocol. Here, we established a protocol for flow cytometric analysis of a single biopsy specimen from the gastrointestinal mucosa and investigated its sensitivity and specificity. DESIGN: In this prospective study, we enrolled patients with previously diagnosed gastrointestinal lymphoma and patients with gastrointestinal lesions that were suspected to be lymphoma. RESULTS: Overall, 15 patients with gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (N=8), duodenal follicular lymphoma (grade 1; N=5), and benign lymphoid hyperplasia (ileum, N=1, and rectum, N=1) were included in this study. Of these, lymphocytes were isolated from 14 patients (93.3%). There were 200,000-1,500,000 viable cells per patient. Biopsy specimens from 10 out of the 12 patients with lymphoma were positive for light chain restriction; the two patients with benign lymphoid hyperplasia showed negative results. CONCLUSIONS: An adequate number of lymphocytes for flow cytometry could be isolated from a single specimen of endoscopic mucosal biopsy from 93.3% of the patients. Overall, the sensitivity of flow cytometric analysis of light chain expression for the diagnosis of B-cell lymphoma was 83.3%, and the specificity was 100%. Although further investigation is required as the sample size of the present study was small, our study suggests a potential option for diagnosing B-cell lymphoma in the gastrointestinal mucosa.

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  • Alterations of lymphocyte count and platelet volume precede cerebrovascular lesions in stroke-prone spontaneously hypertensive rats. International journal

    Takashi Nishinaka, Yui Yamazaki, Atsuko Niwa, Hidenori Wake, Shuji Mori, Tadashi Yoshino, Masahiro Nishibori, Hideo Takahashi

    Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals   25 ( 3 )   305 - 313   2020.5

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    Background: Cerebral small vessel disease (CSVD) is associated with future stroke. Although pathological alteration in small vessels of patients with CSVD can be detected by neuroimaging, diagnosis of CSVD is delayed because it is an asymptomatic disease. The stroke-prone spontaneously hypertensive rat (SHRSP) show similar pathological features to human CSVD and develop stroke-related symptoms with advancing age.Objective: We investigated the time course of haematological parameters in Wistar rats and SHRSP.Material and Methods: Blood cells were analysed using an automated haematological analyser.Results: SHRSP develop stroke-related symptoms including onset of neurological symptoms, decreased body weight and blood brain barrier leakage between 12 and 14 weeks of age. Lymphocyte counts were gradually decreased at 3 weeks before development of stoke-related symptoms and then were further decreased after the development of stroke-related symptoms. The both mean platelet volume and large platelet ratio gradually increased at 3 weeks before the development of stoke-related symptoms. However, although SHRSP showed more microcytic red cells than Wistar rats, the trajectories of change in erythrocyte-related parameters were similar between Wistar rats and SHRSP.Conclusion: Our pilot study suggests that alterations of lymphocyte count and platelet volume predictive indicators for asymptomatic CSVD and symptomatic stroke in SHRSP.

    DOI: 10.1080/1354750X.2020.1750703

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  • MACC1 expression is an indicator of recurrence in early-stage glottic cancer

    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   2020.4

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    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.

    DOI: 10.1093/jjco/hyz206

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

    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   2020.3

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    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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  • 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

    日本病理学会会誌   109 ( 1 )   479 - 480   2020.3

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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

    日本病理学会会誌   109 ( 1 )   479 - 480   2020.3

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  • TAFRO症候群患者における肝臓のCampylobacter jejuni感染症(Hepatic Campylobacter jejuni infection in patients with TAFRO syndrome)

    井川 卓朗, 佐藤 康晴, 吉野 正

    日本病理学会会誌   109 ( 1 )   480 - 480   2020.3

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  • 古典的ホジキンリンパ腫におけるEBV DNAコード化microRNA BART12の欠失(Deletion of EBV DNA encoding microRNA BART12 in classic Hodgkin lymphoma)

    川月 章弘, 井川 卓朗, 田端 哲也, 田中 健大, 吉野 正

    日本病理学会会誌   109 ( 1 )   503 - 503   2020.3

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  • Technique for single-step lymphocyte isolation from an endoscopic biopsy specimen for the diagnosis of gastrointestinal lymphoma. International journal

    Masaya Iwamuro, Takahide Takahashi, Natsuki Watanabe, Sizuma Omote, Katsunori Matsueda, Takehiro Tanaka, Daisuke Ennishi, Fumio Otsuka, Tadashi Yoshino, Hiroyuki Okada

    MethodsX   7   101095 - 101095   2020

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    In this paper, we introduce a simplified, one-step procedure for lymphocyte isolation from an endoscopically biopsied fragment. For lymphocyte isolation, an endoscopically harvested specimen and 5 mL of normal saline solution were placed in a wire mesh strainer set in a porcelain bowl. To obtain the lymphocyte suspension, the solid specimen was crushed using the rubber portion of a plunger of a 10 mL injection syringe. Flow cytometry was performed using the lymphocyte suspension. For validating our methods, the one-step lymphocyte isolation technique was used to perform flow cytometry on samples from 23 patients with (n = 12) or without (n = 11) gastrointestinal lymphoma. Flow cytometry of light chain expression was performed in all patient samples (feasibility: 100%). Sensitivity was 83.3% (10/12) and specificity was 100% (11/11). In conclusion, lymphocytes isolated from a single endoscopic biopsy specimen using our simplified and quick procedure are suitable for flow cytometry. Considering that flow cytometry has an important advantage of providing the results on the examination day itself, the results of this study suggest that flow cytometric analysis using our single-step lymphocyte isolation technique can be potentially used to diagnose lymphoma in the gastrointestinal mucosa. •We introduce a simplified, one-step procedure for lymphocyte isolation from an endoscopically biopsied fragment.•Our technique is feasible for flow cytometric analysis in patients with gastrointestinal lymphoma as well as those with gastrointestinal lesions that are suspected to be lymphoma.

    DOI: 10.1016/j.mex.2020.101095

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  • Triple-negative pleomorphic lobular carcinoma and expression of androgen receptor: Personal case series and review of the literature. International journal

    Kohei Taniguchi, Shinichi Takada, Masako Omori, Takuro Igawa, Midori Filiz Nishimura, Toshiaki Morito, Kouichi Ichimura, Tadashi Yoshino

    PloS one   15 ( 7 )   e0235790   2020

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    Pleomorphic lobular carcinoma (PLC) is a histological variant of invasive lobular carcinoma (ILC) and is associated with worse prognosis than classical ILC. It exhibits a greater degree of cellular atypia and pleomorphism and is occasionally accompanied with apocrine morphology. We investigated the immunohistochemical characteristics of samples from 31 Japanese patients with PLC to elucidate the clinicopathological characteristics of PLC including androgen receptor (AR) immunoreactivity. The surrogate molecular subtypes were luminal A-like, luminal B-like, luminal B-like/HER2, HER2-type, and triple-negative in 5, 4, 3, 5, and 14 cases, respectively. AR was positive in 92.8% (13/14) of the triple-negative PLC cases and 100% (10/10) of the non-triple-negative PLC cases. Disease-specific survival was worse in patients with histological grade 3 PLCs than in those with histological grade 2 PLCs (p = 0.007). However, there was no significant difference in the progression-free survival between the two groups (p = 0.152). No other clinicopathological characteristics were associated with prognosis. These results reveal that PLC exhibits various surrogate molecular subtypes and that the triple-negative subtype frequently expresses AR. The observed molecular apocrine differentiation implicates that triple-negative PLC can be categorized into the luminal AR subtype. Furthermore, AR-targeted therapy might be useful for patients with triple-negative PLC.

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  • Adult T-cell Leukemia-lymphoma with Primary Breast Involvement: A Case Report and Literature Review

    Hiroki Kobayashi, Noboru Asada, Takuro Igawa, Masaya Abe, Yusuke Meguri, Daisuke Ennishi, Hisakazu Nishimori, Nobuharu Fujii, Ken-ichi Matsuoka, Tadashi Yoshino, Yoshinobu Maeda

    Internal Medicine   2020

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    DOI: 10.2169/internalmedicine.5077-20

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

    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   33 ( 12 )   2867 - 2883   2019.12

  • リンパ節生検捺印細胞診が診断の契機となった未分化大細胞型リンパ腫の一例

    宍戸 優, 藤田 健太, 原田 侑香里, 松田 正浩, 永喜多 敬奈, 神農 陽子, 谷口 香, 井川 卓朗, 吉野 正

    岡山県臨床細胞学会誌   38   22 - 26   2019.12

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    背景:左腋窩リンパ節生検において、捺印細胞診が診断の契機となったALK(Anaplastic lymphoma kinase)陽性ALCL(Anaplastic large cell lymphoma)の一例を経験したので報告する。症例:40代、女性。近医にて、発熱および左腋窩リンパ節腫大で経過観察していたが、痛みが出現し、当院血液内科に紹介された。血液検査で可溶性IL-2レセプターが6,764U/mLと高値であり、リンパ節生検が施行された。組織像ではリンパ節の構造は破壊され、中型主体のリンパ腫様細胞が出現し、一部で大型異型細胞が見られた。免疫染色の結果よりT-cell lymphomaが疑われた。リンパ節生検時に作製した捺印細胞診標本では、馬蹄形核やドーナッツ状細胞など多形性に富んだ大型異型細胞が少数孤立散在性に観察された。いわゆるhallmark cellと考えられ、ALCLを疑う所見であった。これを受けて組織標本にて追加免疫染色を施行したところ、CD30、ALK、TIA/GranzymeBが広く陽性を呈した。フローサイトメトリー(以下FCM)および染色体G-band検査の結果と総合し、ALK陽性ALCLと診断された。まとめ:本症例では、組織標本ではALCLに特徴的な異型細胞が少数で観察しづらかったが、捺印細胞診では個々の細胞を詳細に観察することができ、少数であってもhallmark cellと考えられる異型細胞が確認できた。それによりALCLを疑い、FCMや免疫染色などの追加検索に繋がり、診断確定への一助となった。細胞診断を併用することの有用性が改めて認識できた一例であった。(著者抄録)

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  • Histologic Appearance and Immunohistochemistry of DNA Mismatch Repair Protein and p53 in Endometrial Carcinosarcoma: Impact on Prognosis and Insights Into Tumorigenesis. Reviewed

    Saijo M, Nakamura K, Ida N, Nasu A, Yoshino T, Masuyama H, Yanai H

    The American journal of surgical pathology   43 ( 11 )   1493 - 1500   2019.11

  • R-CHOP療法に治療抵抗性を示し外科的治療後に救援化学療法を行い奏効した回腸末端部巨大びまん性大細胞型B細胞リンパ腫

    米山 聖子, 寺崎 靖, 齋藤 勝彦, 西村 碧フィリーズ, 吉野 正

    臨床血液   60 ( 11 )   1577 - 1577   2019.11

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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). Reviewed International journal

    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   2019.10

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    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.

    DOI: 10.1111/pin.12856

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  • Feasibility of flow cytometric analysis of restricted light chain in endoscopic biopsy specimens from patients with gastrointestinal tract B cell lymphoma: a pilot study. International journal

    Katsunori Matsueda, Masaya Iwamuro, Takahide Takahashi, Sizuma Omote, Kenji Nishida, Takehiro Tanaka, Daisuke Ennishi, Fumio Otsuka, Tadashi Yoshino, Hiroyuki Okada

    BMC research notes   12 ( 1 )   571 - 571   2019.9

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    OBJECTIVE: Gastrointestinal tract lymphomas are currently detected more frequently due to advances in endoscopic technology. The aim of this study was to assess the feasibility of flow cytometric analysis of restricted light chain in endoscopic biopsy specimens for the diagnosis of gastrointestinal tract B-cell lymphoma. We prepared viable cell suspensions from unfixed specimens obtained from 10 consecutive patients who had a previous histological diagnosis of gastrointestinal tract B-cell lymphoma. We performed immunophenotypic studies with multi-color flow cytometry and assessed clonality through examination of immunoglobulin light chain expression exclusively in a population identified by anti-CD45 or CD20 antibodies. RESULTS: We could perform light chain expression analysis with 2 endoscopic biopsy specimens from all 10 patients with gastrointestinal tract B-cell lymphoma. We conclude that flow cytometric analysis of endoscopic biopsy specimens is feasible and thus likely useful for the diagnosis of gastrointestinal tract B-cell lymphoma in clinical settings. Trial registration UMIN Clinical Trials Registry, UMIN000027730. Registered 12 June 2017.

    DOI: 10.1186/s13104-019-4578-4

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

    Ikeda T, Gion Y, Yoshino T, Sato Y

    59 ( 2 )   64 - 71   2019.8

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  • KRAS mutations in tongue squamous cell carcinoma. Reviewed

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

    Acta Otolaryngol.   139 ( 7 )   647 - 651   2019.7

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  • 特徴的な組織像を呈したPeripheral T-cell lymphoma with T-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

    日本リンパ網内系学会会誌   59   132 - 132   2019.5

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  • Very rare solitary primary peripheral nerve onset cytotoxic molecule-positive peripheral T-cell lymphoma (PTCL)

    Namiko Matsumoto, Kota Sato, Yoshiaki Takahashi, Yuko Kawahara, Taijun Yunoki, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Toru Yamashita, Maiko Sakamoto, Eisei Kondou, Rei Shibata, Tadashi Yoshino, Toshifumi Ozaki, Koji Abe

    NEUROLOGY AND CLINICAL NEUROSCIENCE   7 ( 3 )   146 - 149   2019.5

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    Here we present the first report of solitary primary peripheral nerve onset cytotoxic molecule (CM)-positive peripheral T-cell lymphoma (PTCL) diagnosed after nerve biopsy. An 84-year-old female with rheumatoid arthritis (RA) complained of asymmetric severe tenderness in her upper limbs. The biopsy pathology revealed a direct invasion of CM-positive PTCL. When RA patients complain of numbness, tenderness, or weakness, lymphomatic peripheral nerve invasion should be considered.

    DOI: 10.1111/ncn3.12280

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  • Methotrexate-associated Lymphoproliferative Disorders of T-cell Phenotype: Clinicopathological Analysis of 28 Cases Reviewed

    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   in press ( 8 )   1135 - 1146   2019.4

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    DOI: 10.1038/s41379-019-0264-2

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  • Methotrexate-associated lymphoproliferative disorder with multiple pulmonary nodules and bilateral cervical lymphadenopathy. Reviewed

    Makihara S, Kariya S, Noujima-Harada M, Ohara N, Naito T, Matsumoto J, Noda Y, Okano M, Yoshino T, Nishizaki K

    Auris, nasus, larynx   2019.2

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

    Kataoka K, Miyoshi H, Sakata S, Dobashi A, Couronné 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   2019.1

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

    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 oto-laryngologica   139 ( 1 )   80 - 84   2019.1

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

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

    Up-regulation of activation-induced cytidine deaminase and its strong expression in extra-germinal centres in IgG4-related disease.   9 ( 1 )   761   2019.1

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  • Long-term spontaneous remission with active surveillance in IgG4-related pleuritis: A case report and literature review. Reviewed

    Makimoto G, Ohashi K, Taniguchi K, Soh J, Taniguchi A, Miyahara N, Toyooka S, Yoshino T, Maeda Y, Kiura K

    Respiratory medicine case reports   28   100938   2019

  • Outcomes after R-CHOP in patients with newly diagnosed advanced follicular lymphoma: a 10-year follow-up analysis of the JCOG0203 trial. Reviewed

    Watanabe T, Tobinai K, Wakabayashi M, Morishima Y, Kobayashi H, Kinoshita T, Suzuki T, Yamaguchi M, Ando K, Ogura M, Taniwaki M, Uike N, Yoshino T, Nawano S, Terauchi T, Hotta T, Nagai H, Tsukasaki K, JCO, Collaborators

    Lancet Haematol. 2018 Nov;5(11):e520-e531.   5 ( 11 )   e520 - e531   2018.11

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  • Identification of TRA-1-60-positive cells as a potent refractory population in follicular lymphomas. Reviewed

    Takata K, Saito K, Maruyama S, Miyata-Takata T, Iioka H, Okuda S, Ling Y, Karube K, Miki Y, Maeda Y, Yoshino T, Steidl C, Kondo E

    Cancer science   110 ( 1 )   443 - 457   2018.11

  • Metabolic abnormalities in adult T-cell leukemia/lymphoma and induction of specific leukemic cell death using photodynamic therapy. Reviewed

    Oka T, Mizuno H, Sakata M, Fujita H, Yoshino T, Yamano Y, Utsumi K, Masujima T, Utsunomiya A

    Scientific reports   8 ( 1 )   14979   2018.10

  • 腎生検にて診断に至った血管内リンパ腫症例(Intravascular lymphoma proven by renal needle biopsy)

    葛目 亜弓, 新谷 大悟, 白石 雄太郎, 花山 宜久, 築地 友紘, 井川 卓朗, 柴田 嶺, 大山 矩史, 鴨井 千尋, 住居 優一, 山本 宜和, 山本 和彦, 近藤 英生, 今城 健二, 吉野 正

    臨床血液   59 ( 9 )   1786 - 1786   2018.9

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  • Watch-and-wait policy versus rituximab-combined chemotherapy in Japanese patients with intestinal follicular lymphoma Reviewed

    Tari, Akira, Kitadai, Yasuhiko, Mouri, Ritsuo, Takigawa, Hidehiko, Asaoku, Hideki, Mihara, Keiichiro, Takata, Katsuyoshi, Fujihara, Megumu, Yoshino, Tadashi, Koga, Tadashi, Fujimori, Shunji, Tanaka, Shinji, Chayama, Kazuaki

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   33 ( 8 )   1461 - 1468   2018.8

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    Background and AimFew reports have demonstrated the effectiveness of treatments for intestinal follicular lymphoma (FL) because of the limited number of patients who undergo comprehensive small intestinal examinations. This study compared the efficacy of rituximab-combined chemotherapy in patients with asymptomatic and low tumor burden (LTB) intestinal FL, according to the criteria of the Groupe d&#039;Etude des Lymphomes Folliculaires, with that of a watch and wait (W&amp;W) approach. MethodsThe endoscopic examination for entire gastrointestinal tracts was performed in 29 Japanese patients with intestinal FL. These patients had CD21-positive follicular dendritic cells arranged in a duodenal pattern. In a prospective, two-center, open-label trial, this study evaluated the efficacy of rituximab-combined chemotherapy ([cyclophosphamide, doxorubicin, vincristine, and prednisone] or [cyclophosphamide, vincristine, and prednisone]) and prolonged treatment with rituximab (R-Chemo+prolongedR) in 14 patients and compared their outcomes with those of 15 patients managed with a W&amp;W approach. ResultsFour patients managed with the W&amp;W plan showed worsening macroscopic findings, lesion area enlargement,

    DOI: 10.1111/jgh.14100

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

    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   2018.7

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

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

    Modern Rheumatology   28 ( 3 )   559 - 563   2018.5

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    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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  • TAFRO症候群を伴う特発性多中心性キャッスルマン病患者の3症例における肝臓Campylobacter jejuni感染症(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

    日本リンパ網内系学会会誌   58   122 - 122   2018.5

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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

    日本リンパ網内系学会会誌   58   120 - 120   2018.5

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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

    日本病理学会会誌   107 ( 1 )   527 - 527   2018.4

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  • Anti-Helicobacter pylori therapy in localized gastric mucosa-associated lymphoid tissue lymphoma: A prospective, nationwide, multicenter study in Japan. Reviewed

    Sugizaki K, Tari A, Kitadai Y, Oda I, Nakamura S, Yoshino T, Sugiyama T

    Helicobacter   23 ( 2 )   e12474   2018.4

  • 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1例

    表 梨華, 田中 健大, 井川 卓朗, 佐藤 康晴, 吉野 正

    日本病理学会会誌   107 ( 1 )   439 - 439   2018.4

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  • Achromobacter Infection Is Rare in Japanese Patients with Pulmonary B-cell Lymphoma. Reviewed

    Aoyama S, Masaki A, Sakamoto Y, Takino H, Murase T, Ohshima K, Yoshino T, Kato S, Inagaki H

    Internal medicine (Tokyo, Japan)   57 ( 6 )   789 - 794   2018.3

  • Gastrointestinal follicular lymphoma: Current knowledge and future challenges. Invited Reviewed

    Takata K, Miyata-Takata T, Sato Y, Iwamuro M, Okada H, Tari A, Yoshino T

    Pathology International   68 ( 1 )   1 - 6   2018.1

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    DOI: 10.1111/pin.12621.

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  • Interleukin-18 Amplifies Macrophage Polarization and Morphological Alteration, Leading to Excessive Angiogenesis. International journal

    Takuro Kobori, Shinichi Hamasaki, Atsuhiro Kitaura, Yui Yamazaki, Takashi Nishinaka, Atsuko Niwa, Shinichi Nakao, Hidenori Wake, Shuji Mori, Tadashi Yoshino, Masahiro Nishibori, Hideo Takahashi

    Frontiers in immunology   9   334 - 334   2018

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    M2 macrophage (Mφ) promotes pathologic angiogenesis through a release of pro-angiogenic mediators or the direct cell-cell interaction with endothelium in the micromilieu of several chronic inflammatory diseases, including rheumatoid arthritis and cancer, where interleukin (IL)-18 also contributes to excessive angiogenesis. However, the detailed mechanism remains unclear. The aim of this study is to investigate the mechanism by which M2 Mφs in the micromilieu containing IL-18 induce excessive angiogenesis in the in vitro experimental model using mouse Mφ-like cell line, RAW264.7 cells, and mouse endothelial cell line, b.End5 cells. We discovered that IL-18 acts synergistically with IL-10 to amplify the production of Mφ-derived mediators like osteopontin (OPN) and thrombin, yielding thrombin-cleaved form of OPN generation, which acts through integrins α4/α9, thereby augmenting M2 polarization of Mφ with characteristics of increasing surface CD163 expression in association with morphological alteration. Furthermore, the results of visualizing temporal behavior and morphological alteration of Mφs during angiogenesis demonstrated that M2-like Mφs induced excessive angiogenesis through the direct cell-cell interaction with endothelial cells, possibly mediated by CD163.

    DOI: 10.3389/fimmu.2018.00334

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

    Omote S, Takata K, Tanaka T, Miyata-Takata T, Ayada Y, Noujima-Harada M, Omote R, Tabata T, Sato Y, Toyokawa T, Kato H, Yagi T, Okada H, Yoshino T

    Medical Molecular Morphology   2018

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

    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   2018

  • Computed tomography findings for diagnosing follicular thyroid neoplasms. Reviewed

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

    Acta Med Okayama   72   577 - 581   2018

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

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

    Acta Medica Okayama   72 ( 1 )   23 - 30   2018

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

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

    Histopathology   2018

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

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

    Scientific Reports   2018

  • Biphenotypic sinonasal sarcomaの1例

    林 詠子, 祇園 由佳, 藤澤 真義, 能島 舞, 田中 顕之, 田中 健大, 柳井 広之, 吉野 正

    診断病理   34 ( 4 )   293 - 298   2017.10

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    患者は50代女性。半年前から徐々に増悪する右鼻閉を訴えていた。画像検査にて頭蓋底に浸潤する右鼻腔・右篩骨洞腫瘤を指摘され、摘出術が施行された。組織学的に上皮下に紡錐形核を有する均一な細胞が束状に増殖しており、staghorn patternを示す血管がみられた。細胞異型や核分裂像に乏しく、壊死はみられなかった。免疫組織化学的に紡錐形細胞はS100蛋白(+)、α-smooth muscle actin(+)、Ki-67陽性率は1%以下であった。電子顕微鏡にて細胞質内にfocal dense plaqueを、RT-PCRにてPAX3-FOXO1融合遺伝子産物が認められた。以上より近年sinonasal tractに発生する新しい腫瘍の一つとして提唱された、biphenotypic sinonasal sarcomaと診断した。(著者抄録)

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  • Triplet therapy with afatinib, cetuximab, and bevacizumab induces deep remission in lung cancer cells harboring EGFR T790M in vivo. Reviewed

    Kudo K, Ohashi K, Makimoto G, Higo H, Kato Y, Kayatani H, Kurata Y, Takami Y, Minami D, Ninomiya T, Kubo T, Ichihara E, Sato A, Hotta K, Yoshino T, Tanimoto M, Kiura K

    Molecular oncology   11 ( 6 )   670 - 681   2017.6

  • 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

    竹内 真衣, 祇園 由佳, 林 詠子, 井川 卓朗, 佐藤 康晴, 吉野 正

    日本リンパ網内系学会会誌   57   110 - 110   2017.5

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  • IgA免疫染色によるIgG4関連疾患と形質細胞型キャッスルマン病の鑑別(IgA immunostaining differentiates IgG4-related disease from plasma cell-type Castleman disease)

    井川 卓朗, 佐藤 康晴, 吉野 正

    日本リンパ網内系学会会誌   57   109 - 109   2017.5

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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

    竹内 真衣, 祇園 由佳, 林 詠子, 井川 卓朗, 佐藤 康晴, 吉野 正

    日本リンパ網内系学会会誌   57   89 - 89   2017.5

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

    Noujima-Harada M, Takata K, Miyata-Takata T, Sakurai H, Igarashi K, Ito E, Nagakita K, Taniguchi K, Ohnishi N, Omote S, Tabata T, Sato Y, Yoshino T

    Cancer science   108 ( 5 )   1071 - 1079   2017.5

  • Gene expression analysis of hypersensitivity to mosquito bite, chronic active EBV infection and NK/T-lymphoma/leukemia. Reviewed

    Kana Washio, Takashi Oka, Lamia Abdalkader, Michiko Muraoka, Akira Shimada, Megumi Oda, Hiaki Sato, Katsuyoshi Takata, Yoshitoyo Kagami, Norio Shimizu, Seiichi Kato, Hiroshi Kimura, Kazunori Nishizaki, Tadashi Yoshino, Hirokazu Tsukahara

    Leuk. Lymphoma   1 - 12   2017.4

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    The human herpes virus, Epstein-Barr virus (EBV), is a known oncogenic virus and plays important roles in life-threatening T/NK-cell lymphoproliferative disorders (T/NK-cell LPD) such as hypersensitivity to mosquito bite (HMB), chronic active EBV infection (CAEBV), and NK/T-cell lymphoma/leukemia. During the clinical courses of HMB and CAEBV, patients frequently develop malignant lymphomas and the diseases passively progress sequentially. In the present study, gene expression of CD16((-))CD56((+))-, EBV((+)) HMB, CAEBV, NK-lymphoma, and NK-leukemia cell lines, which were established from patients, was analyzed using oligonucleotide microarrays and compared to that of CD56(bright)CD16(dim/-) NK cells from healthy donors. Principal components analysis showed that CAEBV and NK-lymphoma cells were relatively closely located, indicating that they had similar expression profiles. Unsupervised hierarchal clustering analyses of microarray data and gene ontology analysis revealed specific gene clusters and identified several candidate genes responsible for disease that can be used to discriminate each category of NK-LPD and NK-cell lymphoma/leukemia.

    DOI: 10.1080/10428194.2017.1304762

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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(IgA immunostaining differentiates IgG4-related disease from plasma cell-type Castleman disease)

    井川 卓朗, 佐藤 康晴, 吉野 正

    日本病理学会会誌   106 ( 1 )   354 - 354   2017.3

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  • Voluntary exercise induces neurogenesis in the hypothalamus and ependymal lining of the third ventricle Reviewed

    Atsuko Niwa, Masahiro Nishibori, Shinichi Hamasaki, Takuro Kobori, Keyue Liu, Hidenori Wake, Shuji Mori, Tadashi Yoshino, Hideo Takahashi

    BRAIN STRUCTURE & FUNCTION   221 ( 3 )   1653 - 1666   2016.4

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    In the adult hypothalamus and ependymal lining of the third ventricle, tanycytes function as multipotential progenitor cells that enable continuous neurogenesis, suggesting that tanycytes may be able to mediate the restoration of homeostatic function after stroke. Voluntary wheel running has been shown to alter neurochemistry and neuronal function and to increase neurogenesis in rodents. In the present study, we found that voluntary exercise improved the survival rate and energy balance of stroke-prone spontaneously hypertensive rats (SHRSP/Kpo). We also investigated the effect of exercise on the proliferation and differentiation of hypothalamic cells using immunoreactivity for tanycytes and neural markers. The proliferation of elongated cells, which may be the tanycytes, was enhanced in exercising SHRSP compared to sedentary rats before and after stroke. In addition, the proliferation of cells was correlated with the induction of fibroblast growth factor-2 in the subependymal cells of the third ventricle and in the cerebrospinal fluid. Some of the newborn cells of exercising SHRSP showed differentiation into mature neurons after stroke. Our results suggest that voluntary exercise correlates with hypothalamic neurogenesis, leading to recovery of homeostatic functions in the adult brain after stroke.

    DOI: 10.1007/s00429-015-0995-x

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  • IgG4関連疾患患者から生じたIgG4産生リンパ腫(IgG4-producing lymphoma arising in a patient with IgG4-related disease)

    井川 卓朗, 佐藤 康晴, 高田 尚良, 吉野 正

    日本病理学会会誌   105 ( 1 )   496 - 496   2016.4

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  • IgG4関連リンパ節症におけるマスト細胞のIgE発現とその意義

    西田 賢司, 竹内 真衣, 片岡 竜貴, 井川 卓朗, 吉野 正, 佐藤 康晴

    日本病理学会会誌   105 ( 1 )   393 - 393   2016.4

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  • 涙腺から発生したと考えられた導管癌の1例 Reviewed

    田中 顕之, 田中 健大, 松本 洋, 柳井 広之, 吉野 正

    診断病理   33 ( 3 )   254 - 258   2016

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

    Miyata-Takata T, Takata K, Toji T, Goto N, Kasahara S, Takahashi T, Tari A, Noujima-Harada M, Miyata T, Sato Y, Yoshino T

    Scientific reports   5   18434   2015.12

  • 成人T細胞白血病リンパ腫に於けるHTLV-1Tax遺伝子発現によるDNAメチル化の一細胞変動 Reviewed

    岡 剛史, 大内田 守, 岡田 康志, 山縣 一夫, 吉野 正

    日本癌学会総会記事   74回   E - 1154   2015.10

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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

    井川 卓朗, 佐藤 康晴, 高田 尚良, 吉野 正

    日本リンパ網内系学会会誌   55   110 - 110   2015.6

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  • Intravascular lymphomaの肺病変に関する検討

    二宮 貴一朗, 藤原 英晃, 前田 嘉信, 高田 尚良, 吉野 正, 木浦 勝行, 谷本 光音

    日本リンパ網内系学会会誌   55   100 - 100   2015.6

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  • 新生CD5陽性のびまん性大細胞型B細胞性リンパ腫はサイクリンD2に対して高い特異性を示す(De novo CD5-positive diffuse large B-cell lymphomas show high specificity for cyclin D2)

    井川 卓朗, 佐藤 康晴, 高田 尚良, 吉野 正

    日本病理学会会誌   104 ( 1 )   494 - 494   2015.3

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  • 成人T細胞白血病リンパ腫に於ける 細胞DNAメチル化の変動解析 Reviewed

    岡 剛史, 大内田 守, 岡田 康志, 上田 潤, 山縣 一夫, 吉野 正

    日本病理学会会誌   104 ( 1 )   494 - 494   2015.3

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  • Acute-phase ITIH4 levels distinguish multi-system from single-system Langerhans cell histiocytosis via plasma peptidomics. Reviewed

    Murakami I, Oh Y, Morimoto A, Sano H, Kanzaki S, Matsushita M, Iwasaki T, Kuwamoto S, Kato M, Nagata K, Hayashi K, Imashuku S, Gogusev J, Jaubert F, Oka T, Yoshino T

    Clinical proteomics   12 ( 1 )   16   2015

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

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

    Modern Rheumatology   2015

  • 成人T細胞白血病リンパ腫に於けるDNAメチル化の動的変動(Dynamic changes of DNA methylation in adult T cell leukemia/lymphoma (ATL)) Reviewed

    岡 剛史, 大内田 守, 岡田 康志, 上田 潤, 山縣 一夫, 吉野 正

    日本癌学会総会記事   73回   E - 1032   2014.9

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  • 非小細胞肺癌におけるF-18 FDG PET/CTの有用性 転移性リンパ節と胸膜浸潤の診断に関して

    新家 崇義, 田中 高志, アラファト・アルキン, 小河 七子, 佐野 由佳, 井田 健太郎, 加藤 勝也, 佐藤 修平, 金澤 右, 宗 淳一, 豊岡 伸一, 三好 新一郎, 田中 健大, 市村 浩一, 吉野 正, 加地 充昌

    Japanese Journal of Radiology   32 ( Suppl. )   61 - 61   2014.2

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  • Lymph node lesions Reviewed

    Yasuharu Sato, Tadashi Yoshino

    Igg4-Related Disease   187 - 193   2014.1

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    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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  • Gastrointestinal Mantle Cell Lymphoma

    OKADA Hiroyuki, OGAWA Masami, MARUNO Atsuko, MINE Tetsuya

    Gastroenterological Endoscopy   55 ( 9 )   "3067 - 78"   2013.9

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    Mantle cell lymphoma (MCL) is a B cell lymphoma derived from the mantle zone of the lymph node follicle. MCL is immunohistochemically positive for CD5 and cyclin D1 and negative for CD10. These markers are useful for a definitive diagnosis. Specific gene abnormalities include a t (11 ; 14) (q13 ; q32) translocation. About 75% of MCL cases are diagnosed at an advanced stage III or IV, with gastrointestinal involvement detected at a high rate.<BR>A review of 71 Japanese patients with gastrointestinal involvement of MCL revealed that 67% were diagnosed at stage IV. Gastrointestinal involvement included stomach (2/3) and colon lesions (2/5). Esophageal involvement was uncommon (4 cases). Stomach lesions varied morphologically, including protruded, ulcerative, and fold-thickening types and multiple lymphomatous polyposis (MLP). MCL is often observed as MLP from the duodenum to the colon.<BR>The prognosis of MCL is poorer among B cell lymphoma cases, with a median survival of 48-68 months. A hyper-CVAD/MA regimen (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high doses of methotrexate and cytarabine) was designed to improve the therapeutic effects of the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) or rituximab plus CHOP. Following this therapy, high-dose chemotherapy with autologous peripheral blood stem cell transplantation is performed to improve the rates of complete remission and relapse-free survival.

    DOI: 10.11280/gee.55.3067

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    Other Link: http://search.jamas.or.jp/link/ui/2014007392

  • Endoscopic Features of Duodenal Involvement in Mantle Cell Lymphoma

    IWAMURO Masaaya, OKAKA Hiroyuki, MORITO Toshiaki, KAWANO Seiji, NASU Junichiro, KAWAHARA Yoshiro, TAKATA Katsuyoshi, YOSHINO Tadashi, YAMAMOTO Kazuhide

    Gastroenterological Endoscopy   55 ( 8 )   "2167 - 74"   2013.8

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    The purpose of this study was to determine the endoscopic features of duodenal involvement in mantle cell lymphoma. Eleven patients with multiple protruding lesions were analyzed in this study. Macroscopically, multiple minute polyploid lesions, verrucous lesions, the mixed type of multiple minute polyploid lesions and verrucous lesions and submucosal tumor-like lesions were observed in 3, 3, 2 and 3 cases respectively. The multiple tiny polyploid lesions were not associated with erosive changes. Meanwhile, all verrucous lesions and submucosal tumor-like lesions presented with an erosive surface except for one verrucous lesion. In order to diagnose mantle cell lymphoma as early as possible, lesions in the duodenum presenting these endoscopic findings need to be biopsied.

    DOI: 10.11280/gee.55.2167

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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   2013.8

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  • Magnifying Endoscopy for Intestinal Follicular Lymphoma Is Helpful for Prompt Diagnosis Reviewed

    Masaya Iwamuro, Masato Okuda, Eiichiro Yumoto, Seiyuu Suzuki, Atsuko Shirakawa, Katsuyoshi Takata, Tadashi Yoshino, Hiroyuki Okada, Kazuhide Yamamoto

    GUT AND LIVER   7 ( 2 )   258 - 261   2013.3

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    The representative endoscopic features of primary intestinal follicular lymphoma are well known as small whitish polypoid nodules, but a magnified view has only been described in a few case reports. Herein, we report a case with intestinal follicular lymphoma in which magnifying endoscopy with narrow band imaging was helpful for prompt diagnosis. A 57-year-old Japanese woman underwent surveillance esophagogastroduodenoscopy. The endoscopic examination revealed confluent whitish granules in the duodenum, distinct from the nodules or polyps that are typical findings of intestinal follicular lymphoma. Magnifying endoscopy visualized whitish enlarged villi, and narrow band imaging emphasized an elongated and coiled vascular pattern. Based on these features, intestinal follicular lymphoma was highly suspected, and subsequent histological study confirmed the diagnosis. This case demonstrates that magnifying endoscopy with narrow band imaging was useful for the detection and prompt diagnosis of intestinal follicular lymphoma. The pathological features of intestinal follicular lymphoma are also discussed. (Gut Liver 2013;7:258-261)

    DOI: 10.5009/gnl.2013.7.2.258

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

    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   2013.2

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  • 非小細胞肺癌におけるF-18 FDG PET/CTの有用性 転移性リンパ節と胸膜浸潤の診断に関して

    田中 高志, 新家 崇義, 井田 健太郎, 加藤 勝也, 佐藤 修平, 宗 淳一, 加地 充昌, 吉野 正, 三好 新一郎, 金澤 右

    日本医学放射線学会学術集会抄録集   72回   S362 - S362   2013.2

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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

  • 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

  • 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.

    Iwaki N, Sato Y, Kurokawa T, Maeda Y, Ohno K, Takeuchi M, Takata K, Orita Y, Nakao S, Yoshino T

    Medical Molecular Morphology   46 ( 3 )   172 - 176   2013

  • Atypical hyaline vascular-type castleman's disease with thrombocytopenia, anasarca, fever, and systemic lymphadenopathy. Reviewed

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

    Journal of clinical and experimental hematopathology : JCEH   53 ( 1 )   87 - 93   2013

  • 胃底腺型胃癌の1例 Reviewed

    田中健大, 市村浩一, 柳井広之, 吉野 正

    診断病理   30 ( 1 )   62 - 65   2013

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  • 小腸原発follicular lymphomaの7例

    岡崎 倫子, 竹本 浩二, 岡 昌平, 濱田 健太, 山崎 泰史, 竹中 龍太, 平良 明彦, 柘野 浩史, 藤木 茂篤, 三宅 孝佳, 吉野 正

    日本消化器病学会雑誌   109 ( 臨増大会 )   A813 - A813   2012.9

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  • IgG4-related perineural disease.

    Sato Y, Yoshino T

    International Journal of Rheumatology   572539   2012

  • 消化管原発濾胞性リンパ腫における十二指腸下降脚病変特殊性(Primary gastrointestinal follicular lymphoma involving the duodenal second portion is a distinct entity)

    高田 尚良, 岡田 裕之, 大宮 直木, 中村 昌太郎, 北台 靖彦, 田利 晶, 赤松 泰次, 吉野 正

    日本癌学会総会記事   70回   461 - 461   2011.9

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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   2011.9

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  • Double translocation lymphoma(DTL)の免疫学的および分子生物学的解析

    菊地 智樹, 菊池 イアーラ幸江, 小島 稔, 安藤 潔, 橋本 優子, 阿部 正文, 高田 尚良, 吉野 正, 富田 直人, 武藤 哲彦, 五十嵐 和彦, 中村 直哉

    日本リンパ網内系学会会誌   51   80 - 80   2011.6

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  • Bach2の過剰発現はDLBCLにおけるIgH-V遺伝子のongoing mutationと関連する(Over-expression of Bach2 is related to ongoing somatic hypermutation of the IgH-V gene of DLBCL)

    菊地 智樹, 小倉 豪, 竹腰 進, 小島 稔, 安藤 潔, 橋本 優子, 阿部 正文, 高田 尚良, 吉野 正, 武藤 哲彦, 五十嵐 和彦, 中村 直哉

    日本癌学会総会記事   69回   163 - 163   2010.8

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  • Tumor formation on the lower eye lid and self-healing papules on the face in a patient with mycosis fungoides Reviewed

    Ai Kajita, Osamu Yamasaki, Shoji Asakura, Ichiro Yamadori, Koichi Ichimura, Tadashi Yoshino

    Nishinihon Journal of Dermatology   72 ( 5 )   473 - 477   2010

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    A 59-year-old man presented with a few year history of multiple erythematous and depigmented patches over the entire body, and was treated with topical steroids. Subsequently, he developed a tumor on his lower eyelid and visited our department Histopathology of a biopsy specimen from the tumor revealed medium to large lymphoid cells throughout the dermis and lymphoid epidermotropism. The patient was diagnosed as stage IIB mycosis fungoides. The tumor was diminished by local radiation therapy and the patches were treated with PUVA therapy. The papules on his face evolved and involuted spontaneously. The development of a tumor and concomitant lymphomatoid papulosis in early stage mycosis fungoides were characteristic. As the large cells of the tumor on the eyelid and papules on the face were positive for CD30, we interpreted the changes of CD30-positive lymphoproliferative disorder as associated with mycosis fungoides.

    DOI: 10.2336/nishinihonhifu.72.473

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  • Aberrations of Genes Regulating NF Kappa B Pathway in B-Cell Malignant Lymphoma Reviewed

    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   2009.11

  • Genome-Wide Analysis of B Cell Non-Hodgkin's Lymphoma Disclosed Frequent Involvement of Genes in NFkB Pathway Reviewed

    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   2008.11

  • 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   2008.11

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    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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  • 喫煙と関連性が低い肺癌マウスモデルに対するゲフィチニブの化学予防効果(Chemopreventive Effect of Gefitinib on Smoking-unrelated Lung Cancer Mouse Model)

    大橋 圭明, 大澤 昌宏, 久保 寿夫, 武田 洋正, 市原 英基, 堀田 勝幸, 平木 章夫, 瀧川 奈義夫, 吉野 正, 田端 雅弘, 高田 穣, 木浦 勝行, 谷本 光音

    日本癌学会総会記事   67回   90 - 90   2008.9

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  • マウスEGFR変異組み換えネズミにおける肺腺癌の発生(Transgenic mice with mouse Egfr mutation developed lung adenocarcinoma)

    大橋 圭明, 木浦 勝行, 頼 冠名, 大澤 昌宏, 平野 世紀, 藤原 義朗, 内田 亜希子, 荻野 敦子, 瀧川 奈義夫, 田端 雅弘, 吉野 正, 高田 穣, 谷本 光音

    日本癌学会総会記事   66回   119 - 119   2007.8

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  • 膵管内乳頭粘液性腺腫の一例 Reviewed

    井上博文, 藤田勝, 今井みどり, 松岡博美, 森下由美子大森昌子, 市村浩一, 大原信哉, 柳井広之, 吉野正

    日本臨床細胞学会岡山支部会誌   25   35 - 36   2006

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  • B細胞性悪性リンパ腫におけるH-cadherin遺伝子領域のLOH解析とDNAメチル化の検討(LOH analysis of 16q24 and prevalent hyper-methylation of the CDH13 gene promoter in malignant B cell lymphomas)

    大釜 陽一郎, 大内田 守, 吉野 正, 伊藤 佐智夫, 石丸 文彦, 原田 実根, 谷本 光音, 清水 憲二

    日本癌学会総会記事   63回   177 - 177   2004.9

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  • Experimental mastoid obliteration by BMP-2/collagen composites Reviewed

    Nishizaki K, Tsujigiwa H, Takeda Y, Yoshino T, Maeta M, Fukushima K, Nagatsuka H, Nagai N

    PROCEEDINGS OF THE 3RD SYMPOSIUM ON MIDDLE EAR MECHANICS IN RESEARCH AND OTOLOGY   121 - 125   2004

  • A columella formation in the middle ear by BMP-2/collagen composites: An experimental study using tissue engineering Reviewed

    Takeda Y, Tsujigiwa H, Nishizaki K, Yoshino T, Orita Y, Nagatsuka H, Nagai N

    PROCEEDINGS OF THE 3RD SYMPOSIUM ON MIDDLE EAR MECHANICS IN RESEARCH AND OTOLOGY   116 - 120   2004

  • An animal model for human EBV-associated hemophagocytic syndrome - Herpesvirus papio frequently induces fatal lymphoproliferative disorders with hemophagocytic syndrome in rabbits Reviewed

    K Hayashi, N Ohara, N Teramoto, S Onoda, HL Chen, T Oka, E Kondo, T Yoshino, K Takahashi, J Yates, T Akagi

    AMERICAN JOURNAL OF PATHOLOGY   158 ( 4 )   1533 - 1542   2001.4

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    Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) Is often associated with fatal infectious mononucleosis. However, the animal model for EBV-AHS has not been developed. We reported the first animal model for EBV-AHS using rabbits infected with EBV-related herpesvirus of baboon (HVP), Eleven of 13 (85%) rabbits inoculated intravenously with HVP-producing cells developed fatal lymphoproliferative disorders (LPD) between 22 and 105 days after Inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in nine of these 11 rabbits, The peroral spray of cell-free HVP induced the virus infection with increased anti-EBV-viral capsid antigen-IgG titers in three of five rabbits, and two of these three infected rabbits died of LPD with HPS, Autopsy revealed hepatosplenomegaly and swollen lymph nodes. Atypical lymphoid T cells expressing EBV-encoded small RNA-I infiltrated diffusely in many organs, frequently involving the lymph nodes, spleen, and liver. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus, HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by polymerase chain reaction or Southern blot analysis. Re-verse transcriptase-polymerase chain reaction revealed both HVP-EBNA1 and HVP-EBNA2 transcripts, suggesting latency type Ri infection. These data indicate that the high rate of rabbit LPD with HPS induction is caused by HVP, This system is useful for studying the pathogenesis, prevention, and treatment of human EBV-AHS.

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  • Programmed cell death in the development of the mouse external auditory canal Reviewed

    Kazunori Nishizaki, Matti Anniko, Yorihisa Orita, Yu Masuda, Tadashi Yoshino, Shigeto Kanda, Junzo Sasaki

    Anatomical Record   252 ( 3 )   378 - 382   1998.11

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    Programmed cell death (PCD) is an essential event for development. The purpose of this work was to ascertain how PCD, in vivo designated apoptosis, is involved in the development of the external auditory canal. We performed a time sequence study of the distribution of apoptosis during the development of external auditory canal (EAC) of the mouse. ICR mice ranging in age from embryonic day 11.5 (E11.5) to 12 days after birth (DAB) were used in the present study. A part of each head including both ears was removed and was processed according to its purpose. Light and electron microscopy for morphological studies and TUNEL method (Gavrieli et al. [1992] J Cell Biol., 119:493-501) for histochemical studies were used. On E11.5, distinct TUNEL- positive staining occurred in the branchial arch. Between E15.5 and 1DAB, TUNEL-positive cells were observed throughout the EAC and the number of these cells decreased with age. On E15.5 and E16.5, numerous TUNEL-positive cells were observed in a cavity remained in the epithelial plate. Transmission electron microscopy revealed that these cells had the features of apoptosis. From 3-12 DAB, no apoptosis was observed in the EAC except for the terminal differentiation of the skin of the EAC. Apoptosis was not observed during recanalization of the EAC, but occurred during the formation of the epithelial plate. The investigation established that PCD is involved in the formation of the epithelial plate, whereas only cornification of the epithelium of the EAC is associated with recanalization.

    DOI: 10.1002/(SICI)1097-0185(199811)252:3<378::AID-AR5>3.0.CO;2-#

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  • Regulation of interleukin-2 receptor gamma chain mRNA expression in human monocytic cell line THP-I Reviewed

    H Yanai, T Yoshino, K Takahashi, Y Ninomiya, T Akagi

    ACTA MEDICA OKAYAMA   50 ( 3 )   145 - 150   1996.6

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    The interleukin-2 receptor (IL-2R) gamma chain (gamma c chain) is shared by IL-4R, IL-7R, IL-9R, and IL-15R and plays an important role in regulation of the immune system. However, its regulation in monocytic cell lines has not been well clarified. We examined the expression and regulation of the IL-2R alpha, IL-2R beta, gamma c chain, IL-4R and IL-7R mRNA in a human monoblastic leukemia cell line, THP-1. Unstimulated THP-1 cells constitutively expressed a low level of gamma c chain and IL-4R mRNA. Phorbol myristate acetate (PMA) induced macrophage-like differentiation and up-regulated the gamma c chain mRNA expression in THP-1 cells. This effect of PMA was suppressed by the protein kinase inhibitors H-7 and staurosporine. PMA did not affect the expression of the other IL-R mRNAs examined. 1 alpha, 25(OH)(2)D-3 and interferon-gamma also induced differentiation of THP-1 cells, but these reagents did not affect the expression of the IL-R mRNAs in THP-1 cells. These findings suggest that the expression of the gamma c chain mRNA is regulated by the PMA-dependent pathway and is not associated with that of the other IL-R mRNAs.

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  • S100 protein-positive T-cell lymphoma ; Report of three cases

    Motoi M, Kitamura Y, Kato M, Akiyoshi H, Ichihara K, Nakamoto S, Yoshino T, Takahashi K, Akagi T

    Yonago Acta Medica   35   127 - 132   1992

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  • Histiocytic Sarcoma(True Histiocytic lymphoma) : Report of a case

    Motoi M, Kitamura Y, Kato M, Akiyoshi H, Ichihara K, Yoshino T

    Yonago Acta Medica   35   231 - 240   1992

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  • MEN 2A (Sipple 症候群) の一例 Reviewed

    長宅 芳男, 橋本 浩三, 平沢 龍登, 槙野 博史, 太田 善介, 大枝 忠史, 大森 弘之, 小松原 正吉, 村上 正和, 吉野 正, Katsuhiko Yoshimoto, 脇谷 勇夫, 三宅 淳史

    腫瘍と感染   Vol.4 ( No.2 )   83 - 89   1991.1

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Books

  • 専門医のための消化器病学 第3版

    下瀬川, 徹, 渡辺, 守(医学), 木下, 芳一, 金子, 周一, 樫田, 博史, 村上, 和成, 安藤, 朗, 糸井, 隆夫(上部消化管のリンパ腫)

    医学書院  2021.11  ( ISBN:9784260045797

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    Total pages:xviii, 710p   Language:Japanese

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  • 大腸癌 第2版

    八尾, 隆史, 菅井, 有(リンパ腫と関連疾患)

    文光堂  2021.4  ( ISBN:9784830622588

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    Total pages:293p   Language:Japanese

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  • 病理組織の見方と鑑別診断 第7版

    吉野, 正, 小田, 義直, 坂元, 亨宇, 森井, 英一, 赤木, 忠厚, 松原, 修, 真鍋, 俊明

    医歯薬出版  2020.12  ( ISBN:9784263731970

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    Total pages:xxii, 740p   Language:Japanese

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  • 別冊日本臨牀 領域別症候群シリーズ 消化管症候群

    日本臨牀  2020.5 

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  • 外科病理学 第5版

    深山, 正久, 森永, 正二郎, 小田, 義直, 坂元, 亨宇, 松野, 吉宏, 森谷, 卓也

    文光堂  2020.4  ( ISBN:9784830604812

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    Total pages:2冊   Language:Japanese

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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

    中外医学社  2019.2  ( ISBN:9784498225169

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    Total pages:xvi, 527p   Language:Japanese

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  • Digestive system tumours

    WHO Classification of Tumours Editorial Board, International Agency for Research on Cancer

    International Agency for Research on Cancer,World Health Organization [distributor]  2019  ( ISBN:9789283244998

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    Total pages:635 p.   Language:English

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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)

    日本リンパ網内系学会

    南江堂  2018.10  ( ISBN:9784524254880

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    Total pages:v, 152p   Language:Japanese

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  • リンパ腫アトラス

    中村, 栄男, 大島, 孝一, 竹内, 賢吾, 田丸, 淳一, 中村, 直哉, 吉野, 正

    文光堂  2018.10  ( ISBN:9784830604799

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    Total pages:xiii, 448p   Language:Japanese

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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

    直江, 知樹, 小松, 則夫, 宮﨑, 泰司, 中村, 栄男, 飯田, 真介, 大島, 孝一, 木下, 朝博, 吉野, 正

    医薬ジャーナル社  2018.10  ( ISBN:9784753228713

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    Total pages:463p   Language:Japanese

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  • 病理組織の見方と鑑別診断第6版

    医歯薬出版  2018.9 

  • 血液細胞アトラス

    通山 薫, 張替 秀郎編

    文光堂  2018.2 

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  • カラー ルービン病理学 改訂版

    西村書店  2017 

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  • インフォームドコンセントのための図説シリーズ 悪性リンパ腫 改訂3版

    医薬ジャーナル社  2017 

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  • WHO classification of Tumours (Reveised 4th Ed)

    IARC Press  2017 

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  • WHO classification of Tumours (Reveised 4th Ed)

    IARC Press  2017 

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  • 血液専門医テキスト改訂第2版

    南江堂  2016 

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  • Hematopathology Second Edition

    Elsevier  2016 

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  • 白血病・リンパ腫薬物療法

    南江堂  2016 

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  • 胃癌第2版

    文光堂  2015 

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  • ルービン基本病理学第5版

    西村書店  2015 

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  • 南山堂医学大辞典 第20版

    南山堂  2015 

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  • 標準病理学第5版

    医学書院  2015 

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  • 悪性リンパ腫治療マニュアル改訂第4版

    南江堂  2015 

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  • 血液疾患診断・治療指針

    中山書店  2015 

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  • リンパ腫アトラス第4版

    文光堂  2014 

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  • IgG4関連腎臓病のすべて

    南江堂  2014 

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  • EBM血液疾患の治療2015-2016

    中外医学社  2014 

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  • 消化器病学第2版

    医学書院  2013 

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  • 悪性リンパ腫 新しい診断と治療のABC 血液9

    最新医学社  2013 

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  • 病理組織の見方と鑑別診断

    松原, 修, 真鍋, 俊明, 吉野, 正, 赤木, 忠厚

    丸善  2013  ( ISBN:9784263200735

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    Total pages:1オンラインリソース   Language:Japanese

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  • 皮膚科臨床アセト13

    中山書店  2012 

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  • IgG4関連疾患アトラス

    前田書店  2012 

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  • リンパ腫セミナー エキスパートによる講義録 日本リンパ網内系学会編

    南江堂  2012 

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  • 平成24年度文部科学省科学研究補助金基盤研究(C)

    文部科学省  2012 

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  • 悪性リンパ腫診療スキルアップ 新津望編

    中外医学社  2012 

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  • 新臨床腫瘍学

    南江堂  2012 

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  • 自己評価型病理学ノート = Master medicine : pathology/systematic pathology

    Bass, Paul, Carr, Norman, Boulay, Clair du, Burroughs, Susan, Way, Claire, 山川, 光徳, 内藤, 善哉, 吉野, 正

    西村書店  2011.11  ( ISBN:9784890134168

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    Total pages:xv, 357p   Language:Japanese

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  • 自己評価型 病理学ノート.

    西村書店  2011 

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  • 悪性リンパ腫の基礎と臨床改訂版

    医薬ジャーナル社  2011 

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  • 血液専門医テキスト

    南江堂  2011 

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  • INTECH

    T-Cell Leukemia  2011 

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  • カラーダイナミック病理学 : 365症例からのアプローチ

    鈴木, 利光, 山川, 光徳, 吉野, 正

    西村書店  2010.12  ( ISBN:9784890134021

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    Total pages:xviii, 1111p   Language:Japanese

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  • WHO血液腫瘍分類リンパ腫系腫瘍

    医薬ジャーナル社  2010 

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  • アトラス細胞診と病理診断

    医学書院  2010 

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  • ダイナミック病理学

    西村書店  2010 

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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・造血器系腫瘍

    文光堂  2010 

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  • 悪性リンパ腫診療ハンドブック

    南江堂  2010 

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  • 血液診療エキスパート 悪性リンパ腫

    中外医学社  2010 

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  • アトラス 細胞診と病理診断

    医学書院  2010 

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  • WHO血液腫瘍分類リンパ腫系腫瘍

    医薬ジャーナル社  2010 

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  • WHO血液腫瘍分類リンパ腫系腫瘍

    医薬ジャーナル社  2010 

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  • WHO血液腫瘍分類リンパ腫系腫瘍

    医薬ジャーナル社  2010 

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  • WHO血液腫瘍分類リンパ腫系腫瘍

    医薬ジャーナル社  2010 

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  • WHO血液腫瘍分類リンパ腫系腫瘍

    医薬ジャーナル社  2010 

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  • ダイナミック病理学

    西村書店  2010 

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  • 症例検討を通して学ぶ悪性リンパ腫診療の実際

    メディカルレヴュー社  2010 

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  • 症例検討を通して学ぶ悪性リンパ腫診療の実際

    メディカルレヴュー社  2010 

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  • 胃癌取り扱い規約第14版

    金原出版  2010 

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  • 造血器腫瘍取り扱い規約第1版

    金原出版  2010 

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  • 病理と臨床 臨時増刊号28巻

    文光堂  2010 

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  • アトラス細胞診と病理診断

    医学書院  2010 

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  • 標準病理学

    医学書院  2010 

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  • 悪性リンパ腫診療ハンドブック

    南江堂  2010 

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  • ダイナミック病理学

    西村書店  2010 

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  • 悪性リンパ腫治療マニュアル

    南江堂  2009  ( ISBN:9784524253166

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  • NEWエッセンシャル病理学第6版

    医歯薬出版  2009  ( ISBN:9784263731123

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  • 人体の構造と機能及び疾患 現代の社会福祉士養成シリーズ

    久美株式会社  2009 

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  • 子宮頚癌

    文光堂  2009 

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  • インフォームドコンセントのための図説シリーズ 悪性リンパ腫 改訂版

    医薬ジャーナル社  2009  ( ISBN:9784753224012

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  • 腫瘍病理鑑別診断アトラス 胃癌

    文光堂  2009  ( ISBN:9784830622243

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  • 悪性リンパ腫臨床と病理

    先端医学社  2009  ( ISBN:9784884075958

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  • 悪性リンパ腫臨床と病理

    先端医学社  2009  ( ISBN:9784884075958

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  • 悪性リンパ腫臨床と病理

    先端医学社  2009  ( ISBN:9784884075958

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  • 悪性リンパ腫臨床と病理

    吉野, 正, 中峯, 寛和, 岡本, 昌隆, 新津, 望

    先端医学社  2009  ( ISBN:9784884075958

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    Total pages:474p   Language:Japanese

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  • 消化管病理標本の読み方

    中村, 眞一, 新井, 冨生, 山野, 泰穂, 海上, 雅光, 大倉, 康男, 和田, 了, 九嶋, 亮治, 菅井, 有, 八尾, 隆史, 吉野, 正, 豊田, 実(医学)

    日本メディカルセンター  2008.10  ( ISBN:9784888752138

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    Total pages:228p   Language:Japanese

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  • 消化管病理標本の読み方 改訂2版

    日本メディカルセンター,東京  2008 

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  • 病理と臨床臨時増刊号

    文光堂,東京  2008 

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  • よくわかる悪性リンパ腫のすべて

    永井書店,東京  2008 

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  • リンパ節・脾・胸線病理画像ケーススタディー

    南山堂,東京  2008 

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  • WHO classification of Tumours (4th Ed)

    IARC Press,東京  2008 

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  • 造血器腫瘍の早期発見・早期診断・モニタリング技術の開発

    岡, 剛史, 吉野, 正, 大内田, 守, 品川, 克至

    岡剛史  2007.3 

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  • 胃MALTリンパ腫の発症因子、除菌反応性を規定する因子の分子病理学的解析

    吉野, 正

    吉野正  2007.3 

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  • カラールービン病理学 臨床医学への基盤

    西村書店  2007 

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  • 平成16?平成18年度科学研究費補助金(基盤研究(B))研究成果報告書

    2007 

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  • 平成17?平成18年度科学研究費補助金(基盤研究(C))研究成果報告書

    2007 

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  • 新皮膚悪性リンパ腫アトラス

    文光堂  2006 

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  • 眼科プラクティス いますぐ役立つ眼病理

    文光堂  2006 

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  • 眼科プラクティス いますぐ役立つ眼病理

    文光堂  2006 

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  • 眼科プラクティス いますぐ役立つ眼病理

    文光堂  2006 

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  • カラーアトラスマクロ病理学

    Cooke, Robin A., Stewart, Brian, RBI, 阿部, 正文, 山川, 光徳, 横井, 豊治, 吉野, 正

    西村書店  2005.12  ( ISBN:4890133399

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    Total pages:ix, 290p   Language:Japanese

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  • 悪性リンパ腫・臨床と病理 平野正美監修 新津望 岡本昌隆 中峯寛和、吉野 正編 各論

    先端医学社  2005 

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  • カラーアトラス マクロ病理学第3版

    西村書店  2005 

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  • マクロ病理学第3版

    西村書店,東京  2005 

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  • 悪性リンパ腫・臨床と病理

    先端医学社,東京  2005 

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  • 基礎組織病理学 第4版

    西村書店,東京  2004 

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  • カラーアトラス 基礎組織病理学 第4版

    西村書店  2004 

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  • 新WHO分類による白血病・リンパ系腫瘍の病態学

    中外医学社,東京  2004 

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  • 新WHO分類による白血病・リンパ系腫瘍の病態学

    中外医学社,東京  2004 

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  • 新WHO分類による白血病・リンパ系腫瘍の病態学

    中外医学社,東京  2004 

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  • インフォームドコンセントのための図説シリーズ 悪性リンパ腫

    医薬ジャーナル社,大阪  2004 

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  • インフォームドコンセントのための図説シリーズ 悪性リンパ腫

    医薬ジャーナル社,大阪  2004 

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  • 最新・悪性リンパ腫アトラス

    文光堂,東京  2004 

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  • 最新・悪性リンパ腫アトラス

    文光堂,東京  2004 

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  • 最新・悪性リンパ腫アトラス

    文光堂,東京  2004 

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  • 最新・悪性リンパ腫アトラス

    文光堂,東京  2004 

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  • 最新・悪性リンパ腫アトラス

    文光堂,東京  2004 

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  • 最新・悪性リンパ腫アトラス

    文光堂,東京  2004 

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  • 最新・悪性リンパ腫アトラス

    文光堂,東京  2004 

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  • 白血病の基礎と臨床

    医薬ジャーナル社,大阪  2004 

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  • 悪性リンパ腫治療マニュアル 改訂第二版

    南江堂  2003 

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  • 「悪性リンパ腫の基礎と臨床」

    医薬ジャーナル社 東京  2003 

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  • 「B細胞非ホジキンリンパ腫治療のストラテジー」

    先端医学社 東京  2003 

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  • 各種病態における非T細胞リンパ球(腫)の皮膚ホーミングレセプター発現の検討

    吉野, 正

    吉野正  2002.3 

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  • リンパ節・脾・胸腺(分担)、「病理組織の見方と鑑別診断」第4版、赤木忠厚、大朏祐治、松原 修編、pp 61-89、医歯薬出版

    医歯薬出版  2002 

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  • 悪性リンパ腫治療の新たなアプローチ

    先端医学社  2001 

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  • 「悪性リンパ腫治療の新たなアプローチ」

    先端医学社、東京  2000 

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  • 「消化管病理標本の読み方」

    日本メディカルセンター、東京  1999 

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  • 腫瘍病理アトラス

    医歯薬出版 

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MISC

  • IRTA-1 expression in B-cell lymphoma

    田端哲也, 井川卓朗, 田中健大, 佐藤康晴, 吉野正

    日本病理学会会誌   110 ( 1 )   2021

  • Spontaneous regression of plasmablastic lymphoma; 2 cases report

    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   39th   2021

  • 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)   60   2021

  • 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   60   2020

  • 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   60   2020

  • PD-L1 expression and clinicopathological analysis in CHL-type MTX-LPD

    祇園由佳, 土井美里, 吉野正, 佐藤康晴

    日本病理学会会誌   109 ( 1 )   2020

  • 腸管原発濾胞性リンパ腫の病態と治療

    田利晶, 北台靖彦, 毛利律生, 瀧川英彦, 麻奥英毅, 三原圭一朗, 吉野正

    日本消化管学会雑誌   4 ( Supplement )   2020

  • Clinicopathological analysis of CD5-positive DLBCL and double-expressor lymphoma

    田端哲也, 佐藤康晴, 佐藤康晴, 吉野正

    日本病理学会会誌   109 ( 1 )   2020

  • Expression of LEF1 in peripheral T-cell lymphoma

    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   109 ( 1 )   2020

  • 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)   59   2020

  • Spontaneous regression of plasmablastic lymphoma; 2 cases report

    池田知佳, 井川卓朗, 吉野正, 佐藤康晴

    日本病理学会会誌   109 ( 1 )   2020

  • 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   60 ( 5 )   392 - 397   2019.5

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    Language:Japanese   Publisher:(一社)日本血液学会-東京事務局  

    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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  • 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   59   141 - 141   2019.5

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  • EBV陽性びまん性大細胞型B細胞リンパ腫に対する化学療法施行後に血管免疫芽球性T細胞リンパ腫を発症した1例

    渡邊 真衣, 水原 健太郎, 遠西 大輔, 阿部 将也, 住居 優一, 浦田 知宏, 藤原 悠紀, 佐伯 恭昌, 廻 勇輔, 淺田 騰, 西森 久和, 松岡 賢市, 藤井 伸治, 吉野 正, 前田 嘉信

    日本リンパ網内系学会会誌   59   153 - 153   2019.5

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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 Invited

    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   2019.4

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  • 濾胞性リンパ腫 Invited

    吉野 正, 田端哲也, 佐藤康晴

    病理と臨床   37 ( 3 )   256 - 261   2019.3

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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

    日本病理学会会誌   108 ( 1 )   2019

  • 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   2018.12

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    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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  • Merkel cell polyomavirus and Langerhans cell neoplasm

    Ichiro Murakami, Ichiro Murakami, Noriko Wada, Junko Nakashima, Junko Nakashima, Mitsuko Iguchi, Mitsuko Iguchi, Makoto Toi, Yumiko Hashida, Tomonori Higuchi, Masanori Daibata, Michiko Matsushita, Takeshi Iwasaki, Satoshi Kuwamoto, Satoshi Kuwamoto, Yasushi Horie, Keiko Nagata, Kazuhiko Hayashi, Takashi Oka, Tadashi Yoshino, Toshihiko Imamura, Akira Morimoto, Shinsaku Imashuku, Jean Gogusev, Francis Jaubert

    Cell Communication and Signaling   16   2018.8

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    © 2018 The Author(s). Background: The relationship between various external agents such as pollen, food, and infectious agents and human sensitivity exists and is variable depending upon individual&#039;s health conditions. For example, we believe that the pathogenetic potential of the Merkel cell polyomavirus (MCPyV), the resident virus in skin, is variable and depends from the degree of individual&#039;s reactivity. MCPyV as well as Epstein-Barr virus, which are normally connected with humans under the form of subclinical infection, are thought to be involved at various degrees in several neoplastic and inflammatory diseases. In this review, we cover two types of Langerhans cell neoplasms, the Langerhans cell sarcoma (LCS) and Langerhans cell histiocytosis (LCH), represented as either neoplastic or inflammatory diseases caused by MCPyV. Methods: We meta-analyzed both our previous analyses, composed of quantitative PCR for MCPyV-DNA, proteomics, immunohistochemistry which construct IL-17 endocrine model and interleukin-1 (IL-1) activation loop model, and other groups&#039; data. Results: We have shown that there were subgroups associated with the MCPyV as a causal agent in these two different neoplasms. Comparatively, LCS, distinct from the LCH, is a neoplastic lesion (or sarcoma) without presence of inflammatory granuloma frequently observed in the elderly. LCH is a proliferative disease of Langerhans-like abnormal cells which carry mutations of genes involved in the RAS/MAPK signaling pathway. We found that MCPyV may be involved in the development of LCH. Conclusion: We hypothesized that a subgroup of LCS developed according the same mechanism involved in Merkel cell carcinoma pathogenesis. We proposed LCH developed from an inflammatory process that was sustained due to gene mutations. We hypothesized that MCPyV infection triggered an IL-1 activation loop that lies beneath the pathogenesis of LCH and propose a new triple-factor model.

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  • Neck metastasis in patients with T1-2 supraglottic cancer

    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   2018.6

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    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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  • Neck metastasis in patients with T1-2 supraglottic cancer

    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   2018.6

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    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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  • Marginal zone B cell lymphoma治療後に、複視を契機にneurolymphomatosisとして再発したと考えられる1例

    松田 真幸, 坂本 真衣子, 碓井 喜明, 藤原 悠紀, 近藤 匠, 谷 勝真, 佐伯 恭昌, 廻 勇輔, 岡本 幸代, 西森 久和, 近藤 英生, 藤井 伸治, 松岡 賢市, 前田 嘉信, 吉野 正

    臨床血液   59 ( 5 )   632 - 632   2018.5

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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   58   110 - 110   2018.5

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  • 乳房腫脹を契機に診断されたperipheral T-cell lymphoma、with T follicular helper phenotypeの1例

    碓井 喜明, 松岡 賢市, 近藤 匠, 坂本 真衣子, 谷 勝真, 藤原 悠紀, 佐伯 恭昌, 廻 勇輔, 淺田 騰, 岡本 幸代, 西森 久和, 近藤 英生, 藤井 伸治, 吉野 正, 前田 嘉信

    臨床血液   59 ( 5 )   633 - 633   2018.5

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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   58   109 - 109   2018.5

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  • Epstein–Barr virus-positive mucocutaneous ulcer in a patient with polycythemia vera treated with oral hydroxyurea

    Toshihisa Hamada, Mariko Kawata, Yoshinobu Maeda, Tadashi Yoshino, Tomoko Miyake, Shin Morizane, Yoji Hirai, Keiji Iwatsuki

    Journal of Dermatology   45 ( 4 )   e82 - e83   2018.4

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    DOI: 10.1111/1346-8138.14127

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  • 頭頸部領域におけるリンパ腫および類縁疾患 Invited

    佐藤康晴, 吉野 正

    病理と臨床   36 ( 4 )   353 - 357   2018.4

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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   107 ( 1 )   441 - 441   2018.4

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  • TypeD(CD8+) lymphomatoid papulosis in a patient with classic (CD4+) mycosis fungoides

    Junko Hori-Kosogabe, Toshihisa Hamada, Shin Morizane, Yoji Hirai, Tomoko Miyake, Tadashi Yoshino, Keiji Iwatsuki

    European Journal of Dermatology   28 ( 2 )   267 - 268   2018.3

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    DOI: 10.1684/ejd.2018.3234

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  • Gastric neuroendocrine tumor arising from heterotopic pancreas

    Takehiro Tanaka, Rika Omote, Noriko Okazaki, Hiroyuki Yanai, Tadashi Yoshino

    Clinical Journal of Gastroenterology   11 ( 1 )   34 - 37   2018.2

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    There are few English reports on secondary tumors from heterotopic pancreas. Here, we describe a case of gastric neuroendocrine tumor (NET) arising from heterotopic pancreas. A 72-year-old woman underwent esophagogastroduodenoscopy as part of a general health check-up. An endoscopic examination revealed a submucosal tumor on the greater curvature of the gastric body. Laparoscopic and endoscopic cooperative surgery was performed. Histological diagnosis concluded that it was a Grade 1 NET arising from heterotopic pancreas. We report this extremely rare case of a NET presenting as a submucosal tumor, considered to have originated from heterotopic pancreatic tissue.

    DOI: 10.1007/s12328-017-0795-3

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  • 骨髄生検で診断に至ったMixed cellularity classical Hodgkin lymphomaの一例

    臼杵 碧フィリーズ, 木村 耕介, 砂田 匠彦, 安田 美帆, 長谷川 功, 岩室 雅也, 花山 宜久, 頼 冠名, 小比賀 美香子, 近藤 英生, 吉野 正, 大塚 文男

    日本病院総合診療医学会雑誌   14 ( 1 )   45 - 45   2018.1

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

    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

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    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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  • Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707

    Yoshinobu Maeda, Hisakazu Nishimori, Isao Yoshida, Yasushi Hiramatsu, Masatoshi Uno, Yasufumi Masaki, Kazutaka Sunami, Taro Masunari, Yuichiro Nawa, Hiromichi Yamane, Hiroshi Gomyo, Tsutomu Takahashi, Tomofumi Yano, Keitaro Matsuo, Koichi Ohshima, Shigeo Nakamura, Tadashi Yoshino, Mitsune Tanimoto

    HAEMATOLOGICA   102 ( 12 )   2097 - 2103   2017.12

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    The standard CHOP therapy for peripheral T-cell lymphoma has resulted in unsatisfactory outcomes and it is still not clear what is the optimal front-line therapy. We conducted a multicenter phase II study of dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone (EPOCH) for untreated peripheral T-cell lymphoma patients. In this prospective study, 41 patients were treated with dose-adjusted-EPOCH as initial therapy: peripheral T-cell lymphoma-not otherwise specified, n=21; angioimmunoblastic T-cell lymphoma, n=17; anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, n=2; and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, n=1. Median patient age was 64 years (range: 3279 years). According to the International Prognostic Index criteria, 51.2% were at high-intermediate or high risk. The overall response and complete response rates were 78.0% [95% confidence interval (CI): 62.4-89.4%] and 61.0% (95% CI: 44.5-75.8%), respectively. At the median follow up of 24.0 months, the 2-year progression-free survival and overall survival were 53.3% (95% CI: 36.4-67.5%) and 73.2% (95% CI: 56.8-84.1%), respectively. The younger patients (&lt;= 60 years old) had a high response rate (overall response 94.1% and complete response 70.6%) and survival rate (progression-free survival 62.5% and overall survival 82.4%). The most common grade &gt;= 3 adverse events were neutropenia (74.5%), anemia (40.8%), thrombocytopenia (22.0%), and febrile neutropenia (9.0%). Dose-adjusted-EPOCH had a high response rate with a tolerable toxicity profile. Our results indicate that dose-adjusted-EPOCH is a reasonable first-line approach for peripheral T-cell lymphoma patients and may improve outcomes.

    DOI: 10.3324/haematol.2017.167742

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  • Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707

    Yoshinobu Maeda, Hisakazu Nishimori, Isao Yoshida, Yasushi Hiramatsu, Masatoshi Uno, Yasufumi Masaki, Kazutaka Sunami, Taro Masunari, Yuichiro Nawa, Hiromichi Yamane, Hiroshi Gomyo, Tsutomu Takahashi, Tomofumi Yano, Keitaro Matsuo, Koichi Ohshima, Shigeo Nakamura, Tadashi Yoshino, Mitsune Tanimoto

    HAEMATOLOGICA   102 ( 12 )   2097 - 2103   2017.12

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    The standard CHOP therapy for peripheral T-cell lymphoma has resulted in unsatisfactory outcomes and it is still not clear what is the optimal front-line therapy. We conducted a multicenter phase II study of dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone (EPOCH) for untreated peripheral T-cell lymphoma patients. In this prospective study, 41 patients were treated with dose-adjusted-EPOCH as initial therapy: peripheral T-cell lymphoma-not otherwise specified, n=21; angioimmunoblastic T-cell lymphoma, n=17; anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, n=2; and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, n=1. Median patient age was 64 years (range: 3279 years). According to the International Prognostic Index criteria, 51.2% were at high-intermediate or high risk. The overall response and complete response rates were 78.0% [95% confidence interval (CI): 62.4-89.4%] and 61.0% (95% CI: 44.5-75.8%), respectively. At the median follow up of 24.0 months, the 2-year progression-free survival and overall survival were 53.3% (95% CI: 36.4-67.5%) and 73.2% (95% CI: 56.8-84.1%), respectively. The younger patients (&lt;= 60 years old) had a high response rate (overall response 94.1% and complete response 70.6%) and survival rate (progression-free survival 62.5% and overall survival 82.4%). The most common grade &gt;= 3 adverse events were neutropenia (74.5%), anemia (40.8%), thrombocytopenia (22.0%), and febrile neutropenia (9.0%). Dose-adjusted-EPOCH had a high response rate with a tolerable toxicity profile. Our results indicate that dose-adjusted-EPOCH is a reasonable first-line approach for peripheral T-cell lymphoma patients and may improve outcomes.

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  • The Usefulness of Colonoscopy for the Detection of Ileal Involvement in Intestinal Follicular Lymphoma Patients

    Masaya Iwamuro, Katsuyoshi Takata, Eiko Hayashi, Seiji Kawano, Sakiko Hiraoka, Yoshiro Kawahara, Tadashi Yoshino, Hiroyuki Okada

    ACTA MEDICA OKAYAMA   71 ( 5 )   391 - 398   2017.10

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    To evaluate the usefulness of colonoscopy for the detection of ileal involvement in patients with intestinal follicular lymphoma, seventeen patients with intestinal follicular lymphoma who underwent colonoscopy and biopsy sampling from the terminal ileum were enrolled. The patients were divided into 2 groups: cases with ileal involvement (n=6) and cases without ileal involvement (n=11). Patients' clinical backgrounds were compared between the two groups. Subsequently, 10 board-certified endoscopists independently evaluated the endoscopic pictures and determined whether the ileum was involved with follicular lymphoma. Infiltration of follicular lymphoma cells were identified in 6 patients (35.3%). Cases with positive ileal involvement were diagnosed with follicular lymphoma at a younger age than were cases without ileal involvement (55.4 +/- 7.4 vs. 68.1 +/- 10.3 years, p=0.011). Macroscopically, in patients with ileal involvement, there were multiple polypoid elevations smaller than 5 mm in 4 cases, single polypoid elevation smaller than 5 mm in 1 case, and single polypoid elevation larger than 5 mm in 1 case. In patients without ileal involvement, there were no lesions in the terminal ileum in 7 cases, and multiple polypoid elevations smaller than 5 mm were seen in 4 cases. The accuracy of the macroscopic evaluation by 10 board-certified endoscopists was 68.8%. Colonoscopy is particularly recommended during the initial workup of patients with follicular lymphoma diagnosed at age &lt;= 60 years. The diagnosis of ileal involvement based on morphology alone is difficult; thus, biopsy and pathologic diagnosis are required for accurate diagnosis.

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  • The Usefulness of Colonoscopy for the Detection of Ileal Involvement in Intestinal Follicular Lymphoma Patients

    Masaya Iwamuro, Katsuyoshi Takata, Eiko Hayashi, Seiji Kawano, Sakiko Hiraoka, Yoshiro Kawahara, Tadashi Yoshino, Hiroyuki Okada

    ACTA MEDICA OKAYAMA   71 ( 5 )   391 - 398   2017.10

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    To evaluate the usefulness of colonoscopy for the detection of ileal involvement in patients with intestinal follicular lymphoma, seventeen patients with intestinal follicular lymphoma who underwent colonoscopy and biopsy sampling from the terminal ileum were enrolled. The patients were divided into 2 groups: cases with ileal involvement (n=6) and cases without ileal involvement (n=11). Patients' clinical backgrounds were compared between the two groups. Subsequently, 10 board-certified endoscopists independently evaluated the endoscopic pictures and determined whether the ileum was involved with follicular lymphoma. Infiltration of follicular lymphoma cells were identified in 6 patients (35.3%). Cases with positive ileal involvement were diagnosed with follicular lymphoma at a younger age than were cases without ileal involvement (55.4 +/- 7.4 vs. 68.1 +/- 10.3 years, p=0.011). Macroscopically, in patients with ileal involvement, there were multiple polypoid elevations smaller than 5 mm in 4 cases, single polypoid elevation smaller than 5 mm in 1 case, and single polypoid elevation larger than 5 mm in 1 case. In patients without ileal involvement, there were no lesions in the terminal ileum in 7 cases, and multiple polypoid elevations smaller than 5 mm were seen in 4 cases. The accuracy of the macroscopic evaluation by 10 board-certified endoscopists was 68.8%. Colonoscopy is particularly recommended during the initial workup of patients with follicular lymphoma diagnosed at age &lt;= 60 years. The diagnosis of ileal involvement based on morphology alone is difficult; thus, biopsy and pathologic diagnosis are required for accurate diagnosis.

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  • Management of gastric mucosa-associated lymphoid tissue lymphoma in patients with extra copies of the MALT1 gene

    Masaya Iwamuro, Ryuta Takenaka, Masahiro Nakagawa, Yuki Moritou, Shunsuke Saito, Shinichiro Hori, Tomoki Inaba, Yoshinari Kawai, Tatsuya Toyokawa, Takehiro Tanaka, Tadashi Yoshino, Hiroyuki Okada

    WORLD JOURNAL OF GASTROENTEROLOGY   23 ( 33 )   6155 - 6163   2017.9

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    AIM
    To identify the clinical features of gastric mucosa-associated lymphoid tissue (MALT) lymphoma with extra copies of MALT1.
    METHODS
    This is a multi-centered, retrospective study. We reviewed 146 patients with MALT lymphoma in the stomach who underwent fluorescence in situ hybridization analysis for t(11; 18) translocation. Patients were subdivided into patients without t(11; 18) translocation or extra copies of MALT1 (Group A, n = 88), patients with t(11; 18) translocation (Group B, n = 27), and patients with extra copies of MALT1 (Group C, n = 31). The clinical background, treatment, and outcomes of each group were investigated.
    RESULTS
    Groups A and C showed slight female predominance, whereas Group B showed slight male predominance. Mean ages and clinical stages at lymphoma diagnosis were not different between groups. Complete response was obtained in 61 patients in Group A (69.3%), 22 in Group B (81.5%), and 21 in Group C (67.7%). Helicobacter pylori (H. pylori) eradication alone resulted in complete remission in 44 patients in Group A and 13 in Group C. In Group B, 14 patients underwent radiotherapy alone, which resulted in lymphoma disappearance. Although the difference was not statistically significant, event-free survival in Group C tended to be inferior to that in Group A (p = 0.10).
    CONCLUSION
    Patients with t(11; 18) translocation should be treated differently from others. Patients with extra copies of MALT1 could be initially treated with H. pylori eradication, similar to patients without t(11; 18) translocation or extra copies of MALT1.

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  • Management of gastric mucosa-associated lymphoid tissue lymphoma in patients with extra copies of the MALT1 gene

    Masaya Iwamuro, Ryuta Takenaka, Masahiro Nakagawa, Yuki Moritou, Shunsuke Saito, Shinichiro Hori, Tomoki Inaba, Yoshinari Kawai, Tatsuya Toyokawa, Takehiro Tanaka, Tadashi Yoshino, Hiroyuki Okada

    WORLD JOURNAL OF GASTROENTEROLOGY   23 ( 33 )   6155 - 6163   2017.9

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    AIM
    To identify the clinical features of gastric mucosa-associated lymphoid tissue (MALT) lymphoma with extra copies of MALT1.
    METHODS
    This is a multi-centered, retrospective study. We reviewed 146 patients with MALT lymphoma in the stomach who underwent fluorescence in situ hybridization analysis for t(11; 18) translocation. Patients were subdivided into patients without t(11; 18) translocation or extra copies of MALT1 (Group A, n = 88), patients with t(11; 18) translocation (Group B, n = 27), and patients with extra copies of MALT1 (Group C, n = 31). The clinical background, treatment, and outcomes of each group were investigated.
    RESULTS
    Groups A and C showed slight female predominance, whereas Group B showed slight male predominance. Mean ages and clinical stages at lymphoma diagnosis were not different between groups. Complete response was obtained in 61 patients in Group A (69.3%), 22 in Group B (81.5%), and 21 in Group C (67.7%). Helicobacter pylori (H. pylori) eradication alone resulted in complete remission in 44 patients in Group A and 13 in Group C. In Group B, 14 patients underwent radiotherapy alone, which resulted in lymphoma disappearance. Although the difference was not statistically significant, event-free survival in Group C tended to be inferior to that in Group A (p = 0.10).
    CONCLUSION
    Patients with t(11; 18) translocation should be treated differently from others. Patients with extra copies of MALT1 could be initially treated with H. pylori eradication, similar to patients without t(11; 18) translocation or extra copies of MALT1.

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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

    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   2017.8

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

    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   2017.8

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    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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  • Triplet therapy with afatinib, cetuximab, and bevacizumab induces deep remission in lung cancer cells harboring EGFR T790M in vivo

    Kenichiro Kudo, Kadoaki Ohashi, Go Makimoto, Hisao Higo, Yuka Kato, Hiroe Kayatani, Yasuko Kurata, Yoichiro Takami, Daisuke Minami, Takashi Ninomiya, Toshio Kubo, Eiki Ichihara, Akiko Sato, Katsuyuki Hotta, Tadashi Yoshino, Mitsune Tanimoto, Katsuyuki Kiura

    MOLECULAR ONCOLOGY   11 ( 6 )   670 - 681   2017.6

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    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the treatment strategy for EGFR-mutant lung cancers; however, resistance usually occurs due to a secondary mutation, T790M, in EGFR. Combination therapy using afatinib and cetuximab has had good results in lung tumors harboring EGFR(T790M) mutations in clinical trials. The effect of bevacizumab, an antivascular endothelial growth factor (VEGF) antibody, combined with EGFR-TKIs has also been investigated. We hypothesized that the dose of afatinib and cetuximab could be reduced by combination with bevacizumab and that the triplet therapy may result in better tumor inhibition with tolerable toxicity. Using a xenograft mouse model with H1975-harboring EGFR(L858R) (+) (T790M) and RPC-9-harboring EGFR(19DEL+ T790M), we tested the efficacy of the triplet therapy with a modified dose of afatinib, cetuximab, and bevacizumab, and compared this therapy to single and double therapies. Triplet therapy with afatinib, cetuximab, and bevacizumab induced pathological complete remission in xenograft tumors with H1975 and RPC-9 cells versus tumors treated with single or double therapies. We saw no body weight loss in the mice. The triple therapy induced a significant reduction in CD31-positive vascular endothelial cells and increased cleaved caspase-3-positive cells in the tumors. This suggests that one mechanism underlying the deep remission could be suppression of neovascularization and induction of apoptosis by intensive inhibition of driver oncoproteins and VEGF. These results highlight the potential of afatinib, cetuximab, and bevacizumab to induce deep remission in tumors harboring EGFR T790M mutations. Therefore, clinical trials of this combination therapy are warranted.

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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

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

    DIAGNOSTIC CYTOPATHOLOGY   45 ( 6 )   547 - 551   2017.6

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    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.

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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

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

    DIAGNOSTIC CYTOPATHOLOGY   45 ( 6 )   547 - 551   2017.6

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    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.

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

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

    CANCER SCIENCE   108 ( 6 )   1271 - 1280   2017.6

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    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.

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

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

    CANCER SCIENCE   108 ( 6 )   1271 - 1280   2017.6

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    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.

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

    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   2017.5

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

    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   2017.5

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    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.

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  • Therapeutic effects of anti-HMGB1 monoclonal antibody on pilocarpine-induced status epilepticus in mice

    Li Fu, Keyue Liu, Hidenori Wake, Kiyoshi Teshigawara, Tadashi Yoshino, Hideo Takahashi, Shuji Mori, Masahiro Nishibori

    SCIENTIFIC REPORTS   7 ( 1 )   120 - 125   2017.4

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    Inflammatory processes in brain tissue have been described in human epilepsy of various etiologies and in experimental models of seizures. High mobility group box-1 ( HMGB1) is now recognized as representative of damage-associated molecular patterns ( DAMPs). In the present study, we focused on whether anti-HMGB1 antibody treatment could relieve status epilepticus-triggered BBB breakdown and inflammation response in addition to the seizure behavior itself. Pilocarpine and methylscopolamine were used to establish the acute seizure model. Anti-HMGB1 mAb showed inhibitory effects on leakage of the BBB, and on the HMGB1 translocation induced by pilocarpine. The expression of inflammation-related factors, such as MCP-1, CXCL-1, TLR-4, and IL-6 in hippocampus and cerebral cortex were down-regulated by anti-HMGB1 mAb associated with the number of activated astrocytes, microglial cells as well as the expression of IL-1 beta. Both hematoxylin & eosin and TUNEL staining showed that the apoptotic cells could be reduced after anti-HMGB1 mAb treatment. The onset and latency of Racine stage five were significantly prolonged in the anti-HMGB1 mAb group. These results suggested that anti-HMGB1 mAb prevented the BBB permeability, reduced HMGB1 translocation while inhibiting the expression of inflammation-related factors, protected against neural cell apoptosis and prolonged Racine stage 5 seizure onset and latency.

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  • Therapeutic effects of anti-HMGB1 monoclonal antibody on pilocarpine-induced status epilepticus in mice

    Li Fu, Keyue Liu, Hidenori Wake, Kiyoshi Teshigawara, Tadashi Yoshino, Hideo Takahashi, Shuji Mori, Masahiro Nishibori

    SCIENTIFIC REPORTS   7 ( 1 )   1179   2017.4

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    Inflammatory processes in brain tissue have been described in human epilepsy of various etiologies and in experimental models of seizures. High mobility group box-1 ( HMGB1) is now recognized as representative of damage-associated molecular patterns ( DAMPs). In the present study, we focused on whether anti-HMGB1 antibody treatment could relieve status epilepticus-triggered BBB breakdown and inflammation response in addition to the seizure behavior itself. Pilocarpine and methylscopolamine were used to establish the acute seizure model. Anti-HMGB1 mAb showed inhibitory effects on leakage of the BBB, and on the HMGB1 translocation induced by pilocarpine. The expression of inflammation-related factors, such as MCP-1, CXCL-1, TLR-4, and IL-6 in hippocampus and cerebral cortex were down-regulated by anti-HMGB1 mAb associated with the number of activated astrocytes, microglial cells as well as the expression of IL-1 beta. Both hematoxylin & eosin and TUNEL staining showed that the apoptotic cells could be reduced after anti-HMGB1 mAb treatment. The onset and latency of Racine stage five were significantly prolonged in the anti-HMGB1 mAb group. These results suggested that anti-HMGB1 mAb prevented the BBB permeability, reduced HMGB1 translocation while inhibiting the expression of inflammation-related factors, protected against neural cell apoptosis and prolonged Racine stage 5 seizure onset and latency.

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  • Diagnostic Value of Dual-time-point F-18 FDG PET/CT and Chest CT for the Prediction of Thymic Epithelial Neoplasms

    Takayoshi Shinya, Takashi Tanaka, Junichi Soh, Toshi Matsushita, Shuhei Sato, Shinichi Toyooka, Tadashi Yoshino, Shinichiro Miyoshi, Susumu Kanazawa

    ACTA MEDICA OKAYAMA   71 ( 2 )   105 - 112   2017.4

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    We retrospectively assessed the dual-time-point (DTP) F-18 FDG PET/CT findings of thymic epithelial neoplasms (TENs) and investigated the diagnostic capacity of PET/CT compared to that of CT for predicting carcinoma. We calculated the ratio of the standardized uptake value of the tumor and that of the aortic arch (T/M ratio) for both the 90-min early scan and the 2-h delayed scan in 56 TEN patients. We used a multivariate logistic regression (MLR) analysis to estimate the CT features of carcinoma. We compared the diagnostic capacities of PET/CT and chest CT using receiver operating characteristic (ROC) analyses. The ROC curve revealed that the appropriate cut-off T/M ratio value for the highest accuracy was 2.39 with 75.0% accuracy. The area under the curve (AUC) was 0.855. The statistical analyses for DTP scans of 35 TEN patients demonstrated 74.3% accuracy and 0.838 AUC for the early scan versus 82.9% and 0.825 for the delayed scan. The MLR analysis indicated that mediastinal fat infiltration was a predictor of carcinoma. The ROC curve obtained for the model yielded an AUC of 0.853. Delayed scanning could improve the diagnostic capacity for carcinoma. The T/M ratio and mediastinal fat infiltration are predictive of carcinoma with moderate diagnostic accuracy.

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  • Diagnostic Value of Dual-time-point F-18 FDG PET/CT and Chest CT for the Prediction of Thymic Epithelial Neoplasms

    Takayoshi Shinya, Takashi Tanaka, Junichi Soh, Toshi Matsushita, Shuhei Sato, Shinichi Toyooka, Tadashi Yoshino, Shinichiro Miyoshi, Susumu Kanazawa

    ACTA MEDICA OKAYAMA   71 ( 2 )   105 - 112   2017.4

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    We retrospectively assessed the dual-time-point (DTP) F-18 FDG PET/CT findings of thymic epithelial neoplasms (TENs) and investigated the diagnostic capacity of PET/CT compared to that of CT for predicting carcinoma. We calculated the ratio of the standardized uptake value of the tumor and that of the aortic arch (T/M ratio) for both the 90-min early scan and the 2-h delayed scan in 56 TEN patients. We used a multivariate logistic regression (MLR) analysis to estimate the CT features of carcinoma. We compared the diagnostic capacities of PET/CT and chest CT using receiver operating characteristic (ROC) analyses. The ROC curve revealed that the appropriate cut-off T/M ratio value for the highest accuracy was 2.39 with 75.0% accuracy. The area under the curve (AUC) was 0.855. The statistical analyses for DTP scans of 35 TEN patients demonstrated 74.3% accuracy and 0.838 AUC for the early scan versus 82.9% and 0.825 for the delayed scan. The MLR analysis indicated that mediastinal fat infiltration was a predictor of carcinoma. The ROC curve obtained for the model yielded an AUC of 0.853. Delayed scanning could improve the diagnostic capacity for carcinoma. The T/M ratio and mediastinal fat infiltration are predictive of carcinoma with moderate diagnostic accuracy.

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

    Akihiro Manabe, Takuro Igawa, Mai Takeuchi, Yuka Gion, Tadashi Yoshino, Yasuharu Sato

    MEDICAL MOLECULAR MORPHOLOGY   50 ( 1 )   34 - 41   2017.3

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    Plasma cell-type Castleman disease (PCD) is often encountered when differentiating IgG4-related disease (IgG4-RD). Given that serum IgA is often elevated in Castleman disease, we investigated whether IgA expression levels in histological specimens can be used to differentiate between the two diseases. Lymph node lesions obtained from 12 IgG4-RD and 11 PCD patients were analysed by immunohistochemistry with anti-IgG, -IgG4, and -IgA antibodies. In addition to all 12 cases of IgG4-RD, 8/11 cases (72.7 %) of PCD also met the diagnostic criteria of IgG4-RD (serum IgG4135 mg/dl and IgG4/IgG-positive cells40 %). IgA-positive cells were sparsely and densely distributed in IgG4-RD and PCD cases, respectively. The median number of IgA-positive cells +/- SD in all 12 cases of IgG4-RD was 31 +/- 37 cells per three high-powered fields (3HPFs) (range 4-118 cells/3HPFs). In contrast, the median number of IgA-positive cells, which was significantly higher in all 11 cases of PCD, was 303 +/- 238 cells/3HPFs (range 74-737 cells/3HPFs) (P &lt; 0.001). In conclusion, our findings indicate that in cases where serum analysis-based data are unavailable, anti-IgA immunostaining can be used for differential diagnosis of IgG4-RD.

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  • Small bowel neoplasms: enhancement patterns and differentiation using post-contrast multiphasic multidetector CT

    Takayoshi Shinya, Ryota Inai, Takashi Tanaka, Noriaki Akagi, Shuhei Sato, Tadashi Yoshino, Susumu Kanazawa

    ABDOMINAL RADIOLOGY   42 ( 3 )   794 - 801   2017.3

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    Purpose: The purpose of the present study was to analyze the enhancement patterns of small bowel neoplasms on post-contrast multiphasic multidetector CT and to assess the diagnostic capacity for differentiating five tumor types.
    Methods: We performed a retrospective study of data on 92 small bowel neoplasms. The neoplasms were categorized into five groups according to pathology findings, not imaging findings (23 adenocarcinomas; 22 lymphomas; 19 metastases; 18 gastrointestinal stromal tumors [GIST]; 10 neuroendocrine tumors [NET]).
    Results: GIST and NET demonstrated a hypervascular pattern in the multiphasic dynamic study. Adenocarcinoma and lymphoma showed a delayed enhancement pattern. Metastasis was classified as an intermediate enhancement pattern. The receiver operating characteristic analyses revealed that attenuation thresholds could be set with acceptable accuracies for most of the small bowel neoplasms.
    Conclusions: Multiphasic dynamic studies may have the potential to improve the diagnostic capacity of multidetector CT for small bowel neoplasms.

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  • Small bowel neoplasms: enhancement patterns and differentiation using post-contrast multiphasic multidetector CT

    Takayoshi Shinya, Ryota Inai, Takashi Tanaka, Noriaki Akagi, Shuhei Sato, Tadashi Yoshino, Susumu Kanazawa

    ABDOMINAL RADIOLOGY   42 ( 3 )   794 - 801   2017.3

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    Purpose: The purpose of the present study was to analyze the enhancement patterns of small bowel neoplasms on post-contrast multiphasic multidetector CT and to assess the diagnostic capacity for differentiating five tumor types.
    Methods: We performed a retrospective study of data on 92 small bowel neoplasms. The neoplasms were categorized into five groups according to pathology findings, not imaging findings (23 adenocarcinomas; 22 lymphomas; 19 metastases; 18 gastrointestinal stromal tumors [GIST]; 10 neuroendocrine tumors [NET]).
    Results: GIST and NET demonstrated a hypervascular pattern in the multiphasic dynamic study. Adenocarcinoma and lymphoma showed a delayed enhancement pattern. Metastasis was classified as an intermediate enhancement pattern. The receiver operating characteristic analyses revealed that attenuation thresholds could be set with acceptable accuracies for most of the small bowel neoplasms.
    Conclusions: Multiphasic dynamic studies may have the potential to improve the diagnostic capacity of multidetector CT for small bowel neoplasms.

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

    Noriko Iwaki, Yuka Gion, Eisei Kondo, Mitsuhiro Kawano, Taro Masunari, Hiroshi Moro, Koji Nikkuni, Kazue Takai, Masao Hagihara, Yuko Hashimoto, Kenji Yokota, Masataka Okamoto, Shinji Nakao, Tadashi Yoshino, Yasuharu Sato

    SCIENTIFIC REPORTS   7   164 - 173   2017.2

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    Multicentric Castleman disease (MCD) is a heterogeneous lymphoproliferative disorder. It is characterized by inflammatory symptoms, and interleukin (IL)-6 contributes to the disease pathogenesis. Human herpesvirus 8 (HHV-8) often drives hypercytokinemia in MCD, although the etiology of HHV-8-negative MCD is idiopathic (iMCD). A distinct subtype of iMCD that shares a constellation of clinical features including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been reported as TAFRO-iMCD, however the differences in cytokine profiles between TAFRO-iMCD and iMCD have not been established. We retrospectively compared levels of serum interferon gamma-induced protein 10 kDa (IP-10), platelet-derived growth factor (PDGF)-AA, interleukin (IL)-10, and other cytokines between 11 cases of TAFRO-iMCD, 6 cases of plasma cell type iMCD, and 21 healthy controls. During flare-ups, patients with TAFRO-iMCD had significantly higher serum IP-10 and tended to have lower PDGF-AA levels than the other 2 groups. In addition, serum IL-10, IL-23, and vascular endothelial growth factor-A were elevated in both TAFRO-iMCD and iMCD. Elevated serum IP-10 is associated with inflammatory diseases including infectious diseases. There was a strong correlation between high serum IP-10 and the presence of TAFRO-iMCD, suggesting that IP-10 might be involved in the pathogenesis of TAFRO-iMCD.

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

    Noriko Iwaki, Yuka Gion, Eisei Kondo, Mitsuhiro Kawano, Taro Masunari, Hiroshi Moro, Koji Nikkuni, Kazue Takai, Masao Hagihara, Yuko Hashimoto, Kenji Yokota, Masataka Okamoto, Shinji Nakao, Tadashi Yoshino, Yasuharu Sato

    SCIENTIFIC REPORTS   7   42316   2017.2

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    Multicentric Castleman disease (MCD) is a heterogeneous lymphoproliferative disorder. It is characterized by inflammatory symptoms, and interleukin (IL)-6 contributes to the disease pathogenesis. Human herpesvirus 8 (HHV-8) often drives hypercytokinemia in MCD, although the etiology of HHV-8-negative MCD is idiopathic (iMCD). A distinct subtype of iMCD that shares a constellation of clinical features including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been reported as TAFRO-iMCD, however the differences in cytokine profiles between TAFRO-iMCD and iMCD have not been established. We retrospectively compared levels of serum interferon gamma-induced protein 10 kDa (IP-10), platelet-derived growth factor (PDGF)-AA, interleukin (IL)-10, and other cytokines between 11 cases of TAFRO-iMCD, 6 cases of plasma cell type iMCD, and 21 healthy controls. During flare-ups, patients with TAFRO-iMCD had significantly higher serum IP-10 and tended to have lower PDGF-AA levels than the other 2 groups. In addition, serum IL-10, IL-23, and vascular endothelial growth factor-A were elevated in both TAFRO-iMCD and iMCD. Elevated serum IP-10 is associated with inflammatory diseases including infectious diseases. There was a strong correlation between high serum IP-10 and the presence of TAFRO-iMCD, suggesting that IP-10 might be involved in the pathogenesis of TAFRO-iMCD.

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  • Clinical outcomes of primary cutaneous anaplastic large cell lymphoma: data from a single Japanese centre.

    Maruta Y, Hamada T, Fukamatsu H, Kaji T, Morizane S, Hirai Y, Miyake T, Yamasaki O, Yoshino T, Iwatsuki K

    Eur J Dermatol.   27 ( 6 )   669 - 671   2017

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

    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

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    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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  • Clinicopathological characteristics and therapeutic strategy in intestinal lymphoma

    Hiroyuki Okada, Takehiro Tanaka, Tadashi Yoshino

    Journal of Japanese Society of Gastroenterology   114 ( 11 )   1957 - 1967   2017

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    DOI: 10.11405/nisshoshi.114.1957

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  • Clinicopathological characteristics and therapeutic strategy in intestinal lymphoma

    Hiroyuki Okada, Takehiro Tanaka, Tadashi Yoshino

    Journal of Japanese Society of Gastroenterology   114 ( 11 )   1957 - 1967   2017

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    DOI: 10.11405/nisshoshi.114.1957

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

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

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

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    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.

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

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

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

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    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.

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  • Gene expression analysis of hypersensitivity to mosquito bite, chronic active EBV infection and NK/T-lymphoma/leukemia

    Kana Washio, Takashi Oka, Lamia Abdalkader, Michiko Muraoka, Akira Shimada, Megumi Oda, Hiaki Sato, Katsuyoshi Takata, Yoshitoyo Kagami, Norio Shimizu, Seiichi Kato, Hiroshi Kimura, Kazunori Nishizaki, Tadashi Yoshino, Hirokazu Tsukahara

    LEUKEMIA & LYMPHOMA   58 ( 11 )   2683 - 2694   2017

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    The human herpes virus, Epstein-Barr virus (EBV), is a known oncogenic virus and plays important roles in life-threatening T/NK-cell lymphoproliferative disorders (T/NK-cell LPD) such as hypersensitivity to mosquito bite (HMB), chronic active EBV infection (CAEBV), and NK/T-cell lymphoma/leukemia. During the clinical courses of HMB and CAEBV, patients frequently develop malignant lymphomas and the diseases passively progress sequentially. In the present study, gene expression of CD16((-))CD56((+))-, EBV(+) HMB, CAEBV, NK-lymphoma, and NK-leukemia cell lines, which were established from patients, was analyzed using oligonucleotide microarrays and compared to that of CD56(bright)CD16(dim/-) NK cells from healthy donors. Principal components analysis showed that CAEBV and NK-lymphoma cells were relatively closely located, indicating that they had similar expression profiles. Unsupervised hierarchal clustering analyses of microarray data and gene ontology analysis revealed specific gene clusters and identified several candidate genes responsible for disease that can be used to discriminate each category of NK-LPD and NK-cell lymphoma/leukemia.

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  • Gene expression analysis of hypersensitivity to mosquito bite, chronic active EBV infection and NK/T-lymphoma/leukemia

    Kana Washio, Takashi Oka, Lamia Abdalkader, Michiko Muraoka, Akira Shimada, Megumi Oda, Hiaki Sato, Katsuyoshi Takata, Yoshitoyo Kagami, Norio Shimizu, Seiichi Kato, Hiroshi Kimura, Kazunori Nishizaki, Tadashi Yoshino, Hirokazu Tsukahara

    LEUKEMIA & LYMPHOMA   58 ( 11 )   2683 - 2694   2017

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    The human herpes virus, Epstein-Barr virus (EBV), is a known oncogenic virus and plays important roles in life-threatening T/NK-cell lymphoproliferative disorders (T/NK-cell LPD) such as hypersensitivity to mosquito bite (HMB), chronic active EBV infection (CAEBV), and NK/T-cell lymphoma/leukemia. During the clinical courses of HMB and CAEBV, patients frequently develop malignant lymphomas and the diseases passively progress sequentially. In the present study, gene expression of CD16((-))CD56((+))-, EBV(+) HMB, CAEBV, NK-lymphoma, and NK-leukemia cell lines, which were established from patients, was analyzed using oligonucleotide microarrays and compared to that of CD56(bright)CD16(dim/-) NK cells from healthy donors. Principal components analysis showed that CAEBV and NK-lymphoma cells were relatively closely located, indicating that they had similar expression profiles. Unsupervised hierarchal clustering analyses of microarray data and gene ontology analysis revealed specific gene clusters and identified several candidate genes responsible for disease that can be used to discriminate each category of NK-LPD and NK-cell lymphoma/leukemia.

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  • The Clinical and Hormonal Characteristics of Primary Adrenal Lymphomas: The Necessity of Early Detection of Adrenal Insufficiency

    Ko Harada, Kosuke Kimura, Masaya Iwamuro, Tomohiro Terasaka, Yoshihisa Hanayama, Eisei Kondo, Eiko Hayashi, Tadashi Yoshino, Fumio Otsuka

    INTERNAL MEDICINE   56 ( 17 )   2261 - 2269   2017

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    Objective To analyze the clinical and endocrine characteristics of patients with primary adrenal lymphoma.
    Patients We retrospectively reviewed the cases of five patients with primary adrenal lymphoma who were treated in our hospital between April 2004 and March 2015. We investigated the characteristics of the clinical and pathological findings, treatment, prognosis and complications of adrenal insufficiency.
    Results Adrenal insufficiency, which was confirmed by the laboratory data at the initial presentation, was observed in two cases. One case was complicated by relative adrenal insufficiency during a course of chemotherapy. The plasma adrenaline and urinary adrenaline levels were decreased in four cases and three cases, respectively. Diffusion MRI was radiologically diagnostic. In all of the cases, the patients were pathologically diagnosed with diffuse large-B cell lymphoma and were treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone)-like chemotherapy. Two patients received central nervous system prophylaxis with high-dose methotrexate. Four of the patients survived and one patient died during the follow-up period.
    Conclusion The early detection of adrenal insufficiency and the administration of an appropriate dose of hydrocortisone are necessary during the course of chemotherapy as well as at the initial manifestation. The exclusion of adrenal dysfunction prior to invasive diagnostic procedures, such as CT-guided needle biopsy, is also critical.

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

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

    ONCOLOGY   93 ( 3 )   204 - 212   2017

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    Objective: We aimed to determine the distribution of tumor-associated macrophages (TAMs) in the development of tongue squamous cell carcinoma (SCC) and to elucidate the role of TAMs in the progression of tongue SCC. Methods: The expression of the macrophage markers nitric oxide synthase, Retnla, and mannose receptor 1 in the development of tongue SCC was longitudinally observed using real-time quantitative polymerase chain reaction. Additionally, an immunohistochemical study using an anti-mannose receptor (MR) antibody was performed. Results: The numbers of both of M1 and M2 macrophages in the tongues of mice treated with 4-nitroquinoline-1-oxide (4NQO) were significantly lower compared with those of normal tongues. The cyclo-oxygenase-2 (COX-2) inhibitor did not prevent cancer progression and did not affect the total number of macrophages in the tongues of 4NQO-treated mice. In the immunohistochemical studies, MR staining was observed in lymphangio-endothelium in the subepithelial area of the tongues. The staining intensity of the MR was significantly stronger in the 4NQO-treated mice compared with that in control mice and 4NQO-treated mice treated with the COX-2 inhibitor. Conclusion: TAMs may not contribute to the development of 4NQO-induced tongue SCC. MR expression is associated with the progression of 4NQO-induced tongue SCC. (C) 2017 S. Karger AG, Basel

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

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

    ONCOLOGY   93 ( 3 )   204 - 212   2017

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    Objective: We aimed to determine the distribution of tumor-associated macrophages (TAMs) in the development of tongue squamous cell carcinoma (SCC) and to elucidate the role of TAMs in the progression of tongue SCC. Methods: The expression of the macrophage markers nitric oxide synthase, Retnla, and mannose receptor 1 in the development of tongue SCC was longitudinally observed using real-time quantitative polymerase chain reaction. Additionally, an immunohistochemical study using an anti-mannose receptor (MR) antibody was performed. Results: The numbers of both of M1 and M2 macrophages in the tongues of mice treated with 4-nitroquinoline-1-oxide (4NQO) were significantly lower compared with those of normal tongues. The cyclo-oxygenase-2 (COX-2) inhibitor did not prevent cancer progression and did not affect the total number of macrophages in the tongues of 4NQO-treated mice. In the immunohistochemical studies, MR staining was observed in lymphangio-endothelium in the subepithelial area of the tongues. The staining intensity of the MR was significantly stronger in the 4NQO-treated mice compared with that in control mice and 4NQO-treated mice treated with the COX-2 inhibitor. Conclusion: TAMs may not contribute to the development of 4NQO-induced tongue SCC. MR expression is associated with the progression of 4NQO-induced tongue SCC. (C) 2017 S. Karger AG, Basel

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  • Epstein-Barr virus-positive mucocutaneous ulcer in a patient with polycythemia vera treated with oral hydroxyurea.

    Hamada T, Kawata M, Maeda Y, Yoshino T, Miyake T, Morizane S, Hirai Y, Iwatsuki K

    J Dermatol.   45 ( 4 )   e82-e83   2017

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  • IgG4関連疾患の病態におけるマスト細胞の関与

    竹内真衣, 吉野 正

    血液内科   75 ( 2 )   188 - 192   2017

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  • リンパ増殖性疾患に対する免疫組織化学染色

    田中健大, 岡崎倫子, 吉野 正

    胃と腸   52 ( 8 )   1031 - 1039   2017

  • B細胞リンパ腫に関するWHO分類2016年改訂のポイント

    竹内真衣, 吉野 正

    血液内科   74 ( 4 )   587 - 592   2017

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

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

    MEDICAL MOLECULAR MORPHOLOGY   49 ( 4 )   243 - 249   2016.12

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    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.

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  • Interaction of cytokeratin 19 head domain and HER2 in the cytoplasm leads to activation of HER2-Erk pathway

    Tomoaki Ohtsuka, Masakiyo Sakaguchi, Hiromasa Yamamoto, Shuta Tomida, Katsuyoshi Takata, Kazuhiko Shien, Shinsuke Hashida, Tomoko Miyata-Takata, Mototsugu Watanabe, Ken Suzawa, Junichi Soh, Chen Youyi, Hiroki Sato, Kei Namba, Hidejiro Torigoe, Kazunori Tsukuda, Tadashi Yoshino, Shinichiro Miyoshi, Shinichi Toyooka

    SCIENTIFIC REPORTS   6 ( 39557 )   1 - 13   2016.12

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    HER2 is a receptor tyrosine kinase and its upregulation via activating mutations or amplification has been identified in some malignant tumors, including lung cancers. Because HER2 can be a therapeutic target in HER2-driven malignancies, it is important to understand the molecular mechanisms of HER2 activation. In the current study, we identified that cytokeratin 19 (KRT19) binds to HER2 at the inside face of plasma membrane. HER2 and KRT19, which were concurrently introduced to a human embryonic kidney 293 T cells, revealed an association with each other and resulted in phosphorylation of HER2 with the subsequent activation of a downstream Erk-associated pathway. A binding assay revealed that both the NH2-terminal head domain of KRT19 and the COOH-terminal domain of HER2 were essential for their binding. To investigate the impact of the interaction between HER2 and KRT19 in lung cancer, we examined their expressions and localizations in lung cancers. We found that KRT19 was highly expressed in HER2-positive lung cancer cells, and KRT19 and HER2 were co-localized at the cell membrane. In conclusion, we found that KRT19 intracellularly binds to HER2, playing a critical role in HER2 activation.

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  • Two Relapsed Stage III Childhood Anaplastic Large Cell Lymphoma Patients with NPM-ALK Fusion in Bone Marrow from Initial Diagnosis

    Yui Kanazawa, Yuka Yamashita, Mitsuhiro Fujiwara, Michiko Muraoka, Kana Washio, Kiichiro Kanamitsu, Hisashi Ishida, Takae Nakano, Miho Yamada, Keizo Horibe, Takehiro Tanaka, Tadashi Yoshino, Akira Shimada

    ACTA MEDICA OKAYAMA   70 ( 6 )   503 - 506   2016.12

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    Childhood anaplastic large cell lymphoma (ALCL) accounts for approx. 10-30 of cases of non-Hodgkin lymphoma, and the ALCL99 study reported 60-75 disease-free survival; however, a relatively high relapse rate was observed (25-30). We report 2 patients with Stage III ALCL who relapsed 6-18 months after the end of ALCL99 chemotherapy. A retrospective molecular analysis identified the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) fusion gene in the first diagnostic bone marrow samples taken from both patients. However, antibodies against the ALK protein appeared to be relatively low in the serum of both patients (x100 and x750). An increase in chemotherapy intensity may be beneficial if Stage III ALCL patients are shown to be NPM-ALK chimera-positive in the first diagnostic bone marrow sample.

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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 )   2016.12

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  • Dose-Adjusted EPOCH Chemotherapy for Untreated Peripheral T-Cell Lymphomas: Multicenter Phase II Trial of West-Jhog PTCL0707

    Yoshinobu Maeda, Hisakazu Nishimori, Yasushi Hiramatsu, Isao Yoshida, Masatoshi Uno, Yasufumi Masaki, Kazutaka Sunami, Taro Masunari, Yuichiro Nawa, Hiroshi Gomyo, Hiromichi Yamane, Tsutomu Takahashi, Tomofumi Yano, Hidetaka Takimoto, Keitaro Matsuo, Tadashi Yoshino, Mitsune Tanimoto

    BLOOD   128 ( 22 )   2016.12

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  • Identification of TRA-1-60-Positive Cells As a Potent Refractory Population in Follicular Lymphomas

    Katsuyoshi Takata, Hidekazu Iioka, Tomoko Miyata-Takata, Yukari Miki, Tadashi Yoshino, Yoshinobu Maeda, Ken Saito, Christian Steidl, Eisaku Kondo

    BLOOD   128 ( 22 )   2016.12

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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 )   2016.12

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

    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   2016.11

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    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.

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

    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   2016.11

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    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.

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

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

    MOLECULAR MEDICINE REPORTS   14 ( 5 )   4622 - 4628   2016.11

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    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.

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

    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   2016.9

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    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.

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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

    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   2016.8

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    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.

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  • Aberrant differential expression of EZH1 and EZH2 in Polycomb repressive complex 2 among B- and T/NK-cell neoplasms

    Lamia Abdalkader, Takashi Oka, Katsuyoshi Takata, Hiaki Sato, Ichiro Murakami, Arie P. Otte, Tadashi Yoshino

    PATHOLOGY   48 ( 5 )   467 - 482   2016.8

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    The Polycomb repressive complex-2 members (EZH2, EED, SUZ12 and EZH1) are important regulators of haematopoiesis, cell cycle and differentiation. Over expression of EZH2 has been linked to cancer metastases and poor prognosis. Detailed information on the expression of other members in normal and neoplastic lymphoid tissue remains to be elucidated. Immunohistochemical and immunofluorescent analyses of 156 samples from haematopoietic neoplasms patients and 27 haematopoietic cell lines were used.
    B-cell neoplasms showed a significant over-expression of EZH2, EED and SUZ12 in the aggressive subtypes compared to the indolent subtypes and normal tissue (p = 0.000-0.046) while expression of EZH1 was decreased in mantle cell lymphoma compared to normal tissue (p = 0.011). T/NK-cell neoplasms also showed significant over expression of EZH2, EED and SUZ12 (p = 0.000-0.002) and decreased expression of EZH1 (p = 0.001) compared to normal cells. EZH2 and EZH1 have opposite expression patterns both in normal and neoplastic lymphoid tissues as well as an opposite relation to Ki-67. These results were supported by western blotting analyses. Immunofluorescent staining revealed a difference in the intracellular localisation of EZH1 compared to other members.
    These evidences suggest that EZH2 and EZH1 are important in the counter-balancing mechanisms controlling proliferation/resting of lymphoid cells. The disruption of the balanced EZH2/EZH1 ratio may play important roles in the pathogenesis of lymphomas.

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  • Detection of Minute Duodenal Follicular Lymphoma Lesions Using Magnifying Endoscopy

    Masaya Iwamuro, Eisei Kondo, Fumio Otsuka, Katsuyoshi Takata, Tadashi Yoshino, Yoshiro Kawahara, Hiroyuki Okada

    ACTA MEDICA OKAYAMA   70 ( 2 )   139 - 144   2016.4

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    Esophagogastroduodenoscopy revealed small duodenal lesions in a 56-year-old Japanese man and a 92-year-old Japanese woman with stage IV follicular lymphoma. Magnifying endoscopy examination revealed tiny white deposits in the second duodenal portion of the former patient and slightly enlarged duodenal villi in the latter. In both cases, biopsy revealed infiltration of follicular lymphoma cells and incipient formation of neoplastic follicles. Here, we discuss the usefulness of magnifying endoscopy and narrow-band imaging for the detection of small duodenal lesions in follicular lymphoma cases.

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  • Soluble form of the receptor for advanced glycation end-products attenuates inflammatory pathogenesis in a rat model of lipopolysaccharide-induced lung injury

    Yasuhisa Izushi, Kiyoshi Teshigawara, Keyue Liu, Dengli Wang, Hidenori Wake, Katsuyoshi Takata, Tadashi Yoshino, Hideo Kohka Takahashi, Shuji Mori, Masahiro Nishibori

    JOURNAL OF PHARMACOLOGICAL SCIENCES   130 ( 4 )   226 - 234   2016.4

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    Acute respiratory distress syndrome (ARDS) is a severe respiratory failure caused by acute lung inflammation. Recently, the receptor for advanced glycation end-products (RAGE) has attracted attention in the lung inflammatory response. However, the function of soluble form of RAGE (sRAGE), which is composed of an extracellular domain of RAGE, in ARDS remains elusive. Therefore, we investigated the dynamics of pulmonary sRAGE and the effects of exogenous recombinant human sRAGE (rsRAGE) under intratracheal lipopolysaccharide (LPS)-induced lung inflammation. Our result revealed that RAGE was highly expressed on the alveolar type I epithelial cells in the healthy rat lung including sRAGE isoform sized 45 kDa. Under LPS-induced injured lung, the release of sRAGE into the alveolar space was increased, whereas the expression of RAGE was decreased with alveolar disruption. Treatment of the injured lung with rsRAGE significantly suppressed the lung edema, the neutrophils infiltration, the release of high mobility group box-1 (HMGB1), and the expressions of TNF-alpha, IL-1 beta and iNOS. These results suggest that the alveolar release of sRAGE may play a protective role against HMGB1 as well as exogenous pathogenassociated molecular patterns. Supplementary therapy with sRAGE may be an effective therapeutic strategy for ARDS. (C) 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license.

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  • Endoscopic detection of the gastric lesions of peripheral T-cell lymphoma

    Masaya Iwamuro, Kosuke Kimura, Eisei Kondo, Takahiro Nada, Eri Nakamura, Katsuyoshi Takata, Takehiro Tanaka, Fumio Otsuka, Tadashi Yoshino, Hiroyuki Okada

    ecancermedicalscience   10   625 - 625   2016.3

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    An 82-year-old Japanese man presented with a gastric involvement of peripheral T-cell lymphoma, not otherwise specified. Although gastrointestinal lesions were not detected on computed tomography, oesophagogastroduodenoscopy revealed a slight elevation of the gastric mucosa, with changes in mucosal colour and the presence of abnormal microvessels. This led to the prompt detection of gastric involvement in lymphoma. This case highlights the usefulness of detailed observation of the gastric mucosa for the endoscopic detection of gastric involvement of peripheral T-cell lymphoma.

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  • The role of "watch and wait'' in intestinal follicular lymphoma in rituximab era

    Akira Tari, Hideki Asaoku, Katsuyoshi Takata, Shunji Fujimori, Shinji Tanaka, Megumu Fujihara, Tadashi Koga, Tadashi Yoshino

    SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY   51 ( 3 )   321 - 328   2016.3

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    Objective: There is no consensus regarding the best treatment for intestinal follicular lymphoma (FL). We used watch and wait for patients with intestinal FL with low-tumor-burden (LTB) criteria and without mass formation causing bowel obstruction. We investigated the overall survival (OS) and time to treatment required (TTR). Methods: Thirty-three intestinal FL patients [clinical stage (CS) I:16, II1:0, II2:7, IV:10; median observation period: 45.5 months, range: 13-110 months] were diagnosed via endoscopy. Detailed clinical and pathological examinations were performed, and neoplastic process behavior was monitored. Results: All of the 33 patients were WHO grade 1. FL lesions in the digestive tract were found frequently in the second-fourth portion of the duodenum in 91% of the patients; 87% of those patients had lesions in a broader area including the small intestine. Two patients had an enlargement of the area of the lesions and a worsening of the macroscopic findings. Three patients had CS progression; however, these remained within the indication for watch and wait. Two patients with transformation into diffuse large B-cell lymphoma received rituximab and chemotherapy, which led to complete remission. The OS was 100%. The time to treatment required (TTR) was 49 months in one patient and 37 months in one patient. Conclusion: Intestinal FL in CS I-IV with broad infiltration of the digestive tract meeting the criteria for LTB had a remarkably slow course. This study suggests that watch and wait is appropriate for the treatment of LTB intestinal FL even in the era of rituximab.

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

    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   2016.3

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    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.

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

    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   2016.2

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    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.

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  • Diagnosis of follicular lymphoma of the gastrointestinal tract: A better initial diagnostic workup

    Masaya Iwamuro, Eisei Kondo, Katsuyoshi Takata, Tadashi Yoshino, Hiroyuki Okada

    WORLD JOURNAL OF GASTROENTEROLOGY   22 ( 4 )   1674 - 1683   2016.1

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    Due to an increasing incidence and more frequent recognition by endoscopists, gastrointestinal follicular lymphoma has been established as a variant of follicular lymphoma. However, due to its rarity, there are no established guidelines on the optimal diagnostic strategy for patients with primary gastrointestinal follicular lymphoma or secondary gastrointestinal involvement of systemic follicular lymphoma. This review offers an overview and pitfalls to avoid during the initial diagnostic workup of this disease entity. Previously reported case reports, case series, and retrospective studies are reviewed and focus on the disease's endoscopic and histological features, the roles of computed tomography and positron emission tomography scanning, the clinical utility of the soluble interleukin-2 receptor, and the possible pathogenesis.

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

    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   2016.1

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    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.

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  • Magnifying Endoscopic Features of Follicular Lymphoma Involving the Stomach: A Report of Two Cases

    Masaya Iwamuro, Katsuyoshi Takata, Seiji Kawano, Nobuharu Fujii, Yoshiro Kawahara, Tadashi Yoshino, Hiroyuki Okada

    CASE REPORTS IN GASTROINTESTINAL MEDICINE   2016   1 - 6   2016

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    A 70-year-old woman presented with follicular lymphoma involving the stomach, duodenum, jejunum, bone, and lymph nodes. Esophagogastroduodenoscopy revealed multiple depressed lesions in the stomach. Examination with magnifying endoscopy showed branched abnormal vessels along with gastric pits, which were irregularly shaped but were preserved. The second case was a 45-year-old man diagnosed with stage II 1 follicular lymphoma with duodenal, ileal, and colorectal involvement, as well as lymphadenopathy of the mesenteric lymph nodes. Esophagogastroduodenoscopy performed six years after the diagnosis revealed multiple erosions in the gastric body and angle. Magnifying endoscopic observation with narrow-band imaging showed that the gastric pits were only partially preserved and were destroyed in most of the stomach. Branched abnormal vessels were also seen. Pathological features were consistent with follicular lymphoma in both cases. The structural differences reported between the two cases appear to reflect distinct pathologies. Disappearance of gastric pits in the latter case seems to result from loss of epithelial cells, probably due to chronic inflammation. In both cases, branched abnormal vasculature was observed. These two cases suggest that magnified observations of abnormal branched microvasculature may facilitate endoscopic detection and recognition of the extent of gastric involvement in patients with follicular lymphoma.

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

    Nishida K, Sogabe Y, Makihara A, Senoo A, Morimoto H, Takeuchi M, Gion Y, Yoshino T, Sato Y

    Mod Rheumatol.   1 - 5   2016

  • 前眼房水に浸潤した節外性NK/T細胞リンパ腫、鼻型の1例

    那須篤子, 市村浩一, 畠 榮, 柳井広之, 藤田 勝, 濱田香菜, 田中健大, 吉野 正

    日本臨牀細胞学会雑誌   15   89 - 93   2016

  • Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan.

    Tomita S, Kikuti YY, Esteban JC, Takata K, Yoshino T, Beà S, Campo E, Nakamura N

    Pathology.   48 ( 1 )   159 - 160   2016

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  • Colorectal Manifestation of Follicular Lymphoma

    Masaya Iwamuro, Hiroyuki Okada, Katsuyoshi Takata, Ryuta Takenaka, Tomoki Inaba, Motowo Mizuno, Haruhiko Kobashi, Shouichi Tanaka, Masao Yoshioka, Eisei Kondo, Tadashi Yoshino, Kazuhide Yamamoto

    INTERNAL MEDICINE   55 ( 1 )   1 - 8   2016

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    Objective Due to their rarity, the endoscopic features and clinical backgrounds of colorectal follicular lymphoma lesions have not yet been fully investigated. The aim of this study was to reveal the characteristics of this disease entity.
    Methods A database search performed at the Department of Pathology of our institute identified 12 follicular lymphoma patients with involvement in the cecum, colon, and/or rectum. Data regarding the endoscopic, radiological, biological, and pathological examinations performed were retrospectively reviewed from their clinical records.
    Results The mean age of the patients (5 men, 7 women) was 58.7 years. Five patients were classified as being Lugano system stage I, while the other seven patients were stage IV. In all of the patients, colorectal follicular lymphoma presented with papular (n=4), polypoid (n=4), and flat elevated lesions (n=4). No erosions or ulcers were seen in any of the lesions. The initial pathological diagnoses included extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (n=2) and colitis/proctitis with infiltration of inflammatory cells (n=3), in addition to the correct diagnosis of follicular lymphoma (n=7).
    Conclusion Colorectal involvement of follicular lymphoma shows no erosions or ulcers. These lesions could be macroscopically observed as papular, polypoid and flat elevated lesions. Making a correct diagnosis of this disease based on the findings of biopsied samples is sometimes challenging. In such cases, multiple biopsies and/or endoscopic mucosal resection is required, in addition to appropriate consultation with pathologists.

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  • Langerhans Cell Histiocytosis and Langerhans Cell Sarcoma: Current Understanding and Differential Diagnosis.

    Nakamine H, Yamakawa M, Yoshino T, Fukumoto T, Enomoto Y, Matsumura I

    J Clin Exp Hematop.   56 ( 2 )   109 - 118   2016

  • 消化管原発濾胞性リンパ腫の分子生物学的特徴と臨牀病態

    高田尚良, 吉野 正

    血液内科   72   16 - 20   2016

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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

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  • ATLおよびT細胞リンパ腫における遺伝子変異プロファイルの解析

    綿谷陽作, 佐藤康晴, 西田賢司, 三好寛明, 永田安伸, 北中明, 白石友一, 高折晃史, 宮野悟, 松岡雅雄, 渡邉俊樹, 下田和哉, 大島孝一, 吉野正, 小川誠司, 片岡圭亮

    日本HTLV‐1学会学術集会   3rd   57   2016

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  • Histidine-Rich Glycoprotein Prevents Septic Lethality through Regulation of Immunothrombosis and Inflammation.

    Wake H, Mori S, Liu K, Morioka Y, Teshigawara K, Sakaguchi M, Kuroda K, Gao Y, Takahashi H, Ohtsuka A, Yoshino T, Morimatsu H, Nishibori M

    EBioMedicine   9   180 - 194   2016

  • Asymptomatic tracheal MALT lymphoma discovered on spirometric findings presenting with elevated respiratory resistance

    Naoki Kadota, Tsutomu Shinohara, Hisanori Machida, Hirofumi Nakanishi, Fumie Suehiro, Hiroko Toda, Tadashi Yoshino, Fumitaka Ogushi

    BMC Research Notes   8 ( 1 )   2015.12

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    Background: Central airway obstruction (CAO) may be caused by various etiologies. However, conventional chest X-rays are rarely diagnostic for patients with CAO. Case presentation: We here described a 64-year-old asymptomatic female with tracheal mucosa-associated lymphoid tissue lymphoma discovered on spirometric findings during a complete physical examination. The plateau of forced expiratory flow was consistent with CAO. A decreased peak expiratory flow rate was noted at least 3 years before the diagnosis, and was attributed to an insufficient effort by the patient. Impulse oscillometric measurements, which were taken during quiet breathing and were effort-independent, suggested elevated respiratory resistance. These abnormalities completely disappeared after radiation therapy. Conclusion: The addition of impulse oscillometry to spirometry may be useful for screening CAO in routine health examinations.

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  • Prognostic Significance of EBV Association in Diffuse Large B-Cell Lymphoma in the Rituximab Era

    Nozomi Niitsu, Naoki Takahashi, Tadashi Yoshino, Masataka Okamoto, Shigeo Nakamura

    BLOOD   126 ( 23 )   2015.12

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  • Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan

    Sakura Tomita, Yara Y. Kikuti, Joaquim Carreras, Minoru Kojima, Kiyoshi Ando, Hirotaka Takasaki, Rika Sakai, Katsuyoshi Takata, Tadashi Yoshino, Silvia Bea, Elias Campo, Naoya Nakamura

    MODERN PATHOLOGY   28 ( 10 )   1286 - 1296   2015.10

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    Enteropathy-associated T-cell lymphoma (EATL) is a rare primary T-cell lymphoma of the digestive tract. EATL is classified as either Type I, which is frequently associated with and thought to arise from celiac disease and is primarily observed in Northern Europe, and Type II, which occurs de novo and is distributed all over the world with predominance in Asia. The pathogenesis of EATL in Asia is unknown. We aimed to clarify the histological and genomic profiles of EATL in Japan in a homogeneous series of 20 cases. The cases were characterized by immunohistochemistry, high-resolution oligonucleotide microarray, and fluorescence in situ hybridization (FISH) at five different loci: 1q21.3 (CKS1B), 6q16.3 (HACE1), 7p22.3 (MAFK), 9q33.3 (PPP6C), and 9q34.3 (ASS1, CARD9) using formalin-fixed paraffin-embedded sections. The histological appearance of EATL ranged from medium-to large-sized cells in 13 cases (65%), small-to medium-sized cells in five cases (25%), and medium-sized in two cases (10%). The immunophenotype was CD2(+) (60%), CD3 epsilon(+) (100%), CD4(+) (10%), CD7(+) (95%), CD8(+) (80%), CD56(+) (85%), TIA-1(+) (100%), Granzyme B+ (25%), T-cell receptor (TCR)beta(+) (10%), TCR gamma(+) (35%), TCR gamma delta(+) (50%), and double negative for TCR (six cases, 30%). All cases were EBER-. The genomic profile showed recurrent copy number gains of 1q32.3, 4p15.1, 5q34, 7q34, 8p11.23, 9q22.31, 9q33.2, 9q34.13, and 12p13.31, and losses of 7p14.1. FISH showed 15 patients (75%) with a gain of 9q34.3 with good correlation with array comparative genomic hybridization. EATL in Japan is characterized by non-monomorphic cells with a cytotoxic CD8(+) CD56(+) phenotype similar to EATL Type II. The genomic profile is comparable to EATL of Western countries, with more similarity to Type I (gain of 1q and 5q) rather than Type II (gain of 8q24, including MYC). The 9q34.3 gain was the most frequent change confirmed by FISH irrespective of the cell origin of alpha beta-T-cells and gamma delta-T-cells.

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

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

    DIAGNOSTIC PATHOLOGY   10 ( 1 )   185 - 185   2015.10

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

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

    DIAGNOSTIC PATHOLOGY   10 ( 1 )   183 - 183   2015.10

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    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.

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  • Primary Duodenal Follicular Lymphoma Treated With Rituximab Monotherapy and Followed-up for 15 Years

    Anna Seki, Masaya Iwamuro, Masao Yoshioka, Nobuharu Fujii, Hiroyuki Okada, Soichiro Nose, Katsuyoshi Takata, Tadashi Yoshino, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA   69 ( 5 )   301 - 306   2015.10

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    A 41-year-old woman was diagnosed with duodenal follicular lymphoma. She had no other lesions and was assigned to a "watch and wait" policy. Swelling of the inguinal lymph nodes appeared 45 months later, and rituximab monotherapy resulted in complete remission. However, follicular lymphoma recurred in the stomach, rectum and mesenteric and external iliac lymph nodes 81 months after the therapy. The patient received rituximab monotherapy again and has remained in complete remission in the fifteenth year after the initial diagnosis. This case suggests the usefulness of rituximab monotherapy in the long-term management of intestinal follicular lymphoma.

    DOI: 10.18926/AMO/53676

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  • Pediatric diffuse large B-cell lymphoma in Japan

    Atsuko Nakazawa, Tomoo Osumi, Masahito Tsurusawa, Roji Kobayashi, Hideto Iwafuchi, Kouich Ohshima, Jun-Ichi Tamaru, Hirokazu Nakamine, Shigeo Nakamura, Jun-Ichiro Fujimoto, Hiroshi Hojo, Yoshihiro Matsuno, Tadashi Yoshino, Wolfram Klapper

    BRITISH JOURNAL OF HAEMATOLOGY   171   64 - 64   2015.10

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  • A patient with elderly-onset atypical hydroa vacciniforme with an indolent clinical course

    H. Nomura, H. Suzuki, S. Egami, T. Yokoyama, M. Sugiura, K. Tomita, M. Imada, K. Taniguchi, T. Yoshino, K. Iwatsuki

    BRITISH JOURNAL OF DERMATOLOGY   173 ( 3 )   801 - 805   2015.9

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    Hydroa vacciniforme (HV) is a rare photodermatosis that mainly affects children and manifests as vesiculopapular eruptions in sun-exposed areas without systemic symptoms. HV-like lymphoma (HVLL) is one of the Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD) of childhood. Its diagnosis is based on monoclonal T-cell proliferation; however, its degree of malignancy is controversial owing to its variable prognosis. Elderly-onset cases of these diseases are extremely rare, and the clinical features remain unknown. It has been shown that late onset is closely associated with a severe phenotype in EBV-associated LPD including atypical HV. Here we describe a case of elderly-onset atypical HV accompanied by T-cell monoclonality, but with a very indolent clinical course. Our patient indicates a possible case with elderly-onset atypical HV manifesting a favourable course, and that T-cell monoclonality and age of onset cannot always predict the disease severity, and highlights the difficulty of prognosis prediction in elderly-onset atypical HV.

    DOI: 10.1111/bjd.13893

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

    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   2015.9

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    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

    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   2015.8

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    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.

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

    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   2015.8

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    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

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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

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

    CYTOPATHOLOGY   26 ( 4 )   250 - 255   2015.8

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    BackgroundMethods for determining the origin of BK virus (BKV)-infected cells (decoy cells) in clinical urine samples have not been established although they could enhance the diagnosis of BKV infection in immunocompromised patients.
    MethodsWe performed simultaneous immunostaining with anti-S100P (a urothelial marker) and anti-SV40 antibodies in 66 clinical urine samples exhibiting SV40 positivity and a decoy-cell appearance on Papanicolaou staining. The clinical voided urine samples included seven cases of renal transplantation, 47 cases of cancer therapy and 12 cases of non-neoplastic disease. SurePath liquid-based cytology was used for the urine samples.
    ResultsBKV-infected cells were categorized as SV40(+)/S100P(+) and SV40 (+)/S100p(-). SV40(+)/S100P(-) cells were found in 55 cases (83.4%); nine cases (13.6%) carried both SV40(+)/S100P(-) and SV40(+)/S100P(+) cells. The former were identified as BKV infection in renal tubules and the latter in both the renal tubules and urothelial epithelia. The remaining two cases (3.0%) had only SV40(+)/S100P(+) cells of urothelial origin.
    ConclusionSimultaneous immunostaining with anti-S100P and anti-SV40 is a useful method for determining the origin of BKV-infected cells in clinical urine samples from immunocompromised patients such as renal transplantation recipients.

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  • A multicenter survey of enteroscopy for the diagnosis of intestinal follicular lymphoma

    Masaya Iwamuro, Hiroyuki Okada, Seiji Kawano, Junji Shiode, Ryuta Takenaka, Atsushi Imagawa, Tomoki Inaba, Seiyu Suzuki, Mamoru Nishimura, Motowo Mizuno, Masashi Araki, Tomohiko Mannami, Toru Ueki, Haruhiko Kobashi, Haruka Fukatsu, Shouichi Tanaka, Akiyoshi Omoto, Yoshinari Kawai, Takashi Kitagawa, Tatsuya Toyokawa, Katsuyoshi Takata, Tadashi Yoshino, Akinobu Takaki, Kazuhide Yamamoto

    ONCOLOGY LETTERS   10 ( 1 )   131 - 136   2015.7

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    The importance of enteroscopy examinations to investigate the entire length of the small intestines has been emphasized in follicular lymphoma patients with intestinal involvement. The aim of the present study was to determine the current state of enteroscopy examinations, including the performance rate, and the prevalence of small intestinal lesions in a patient population in Japan. A retrospective multicenter survey of 17 institutions collected the case information of 110 follicular lymphoma patients with gastrointestinal involvement. The results of the enteroscopy examinations were reviewed, and in order to identify potential factors affecting the performance rate of enteroscopy, patient gender, age at lymphoma diagnosis, histopathological grade, clinical stage, the date of the initial diagnosis and the annual volume of enteroscopy at the institution were compared between the patients who underwent one or more enteroscopy procedures and the patients who did not undergo enteroscopy. A total of 34 patients (30.9%) underwent enteroscopy, and 24 of these (70.6%) presented with involvement in the jejunum and/or ileum. It was found that more patients diagnosed in recent years and more patients treated at an ultra-high volume institution (101 enteroscopy examinations/year) underwent an enteroscopy. In conclusion, although the prevalence of small intestinal lesions was high (70.6%) in the follicular lymphoma patients presenting with intestinal involvement, the performance rate of enteroscopy was only 30.9%, and thus the majority of the patients have not undergone enteroscopy examinations. Further investigation is required to define the clinical significance of enteroscopy at the initial diagnostic work-up and during the follow-up period of these patients.

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  • イマチニブ療法に対して難治性であったRosai-Dorfman病の2症例 症例報告と文献考察(Two cases of Rosai-Dorfman Disease refractory to Imatinib therapy: Case report and review of literature)

    谷 勝真, 藤井 伸治, 石川 立則, 山本 宣和, 塩手 康弘, 佐伯 恭昌, 清家 圭介, 三道 康永, 中村 真, 藤原 英晃, 西森 久和, 松岡 賢市, 近藤 英生, 前田 嘉信, 谷本 光音, 高田 尚良, 吉野 正

    日本リンパ網内系学会会誌   55   97 - 97   2015.6

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  • 中枢神経原発リンパ腫に対する非照射治癒を目指した移植併用超大量化学療法

    市川 智継, 近藤 英生, 黒住 和彦, 大谷 理浩, 前田 嘉信, 吉野 正, 谷本 光音, 伊達 勲

    日本リンパ網内系学会会誌   55   92 - 92   2015.6

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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   2015.6

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  • 【腸管悪性リンパ腫】 臨床 Mantle cell lymphoma

    岡田 裕之, 岩室 雅也, 田中 健大, 近藤 英生, 吉野 正

    Intestine   19 ( 3 )   260 - 267   2015.5

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    Mantle cell lymphoma(MCL)はリンパ濾胞のマントル層を構成するB細胞性リンパ腫である.遺伝子異常としてはt(11;14)(q13;q32)転座がある.約75%が診断時にすでにIII/IV期の進行期であると報告されており,消化管浸潤は高率に認められる.腸管病変としてはmultiple lymphomatous polyposisを呈する場合が多い.MCLの生存率の中央値は48〜68ヵ月と報告されている.通常のCHOP療法,あるいはリツキシマブ併用CHOP療法の治療強度を高めるためにhyper-CVAD/MA療法が考案され,長期生存がみられている.また,本治療後に自己末梢血幹細胞移植併用の大量化学療法を行うことにより,完全寛解率,無再発生存率が向上することが報告されている.(著者抄録)

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  • Cytokeratin-positive Fibroblastic Reticular Cell Tumor With Follicular Dendritic Cell Features A Case Report and Review of the Literature

    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   2015.4

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    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
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    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.

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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   2015.3

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  • Magnified Endoscopic Features of Duodenal Follicular Lymphoma and Other Whitish Lesions

    Masaya Iwamuro, Hiroyuki Okada, Katsuyoshi Takata, Yoshinari Kawai, Seiji Kawano, Junichiro Nasu, Yoshiro Kawahara, Takehiro Tanaka, Tadashi Yoshino, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA   69 ( 1 )   37 - 44   2015.2

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    The sensitivity and specificity of magnified endoscopic features for differentiating follicular lymphoma from other diseases with duodenal whitish lesions have never been investigated. Here we compared the magnified endoscopic features of duodenal follicular lymphoma with those of other whitish lesions. We retrospectively reviewed the cases of patients with follicular lymphoma (n = 9), lymphangiectasia (n = 7), adenoma (n = 10), duodenitis (n = 4), erosion (n = 1), lymphangioma (n = 1), and hyperplastic polyp (n = 1). The magnified features of the nine follicular lymphomas included enlarged villi (n = 8), dilated microvessels (n = 5), and opaque white spots of various sizes (n = 9). The lymphangiectasias showed enlarged villi, dilated microvessels, and white spots, but the sizes of the white spots were relatively homogeneous and their margin was clear. Observation of the adenoma and duodenitis revealed only whitish villi. Although the lymphangioma was indistinguishable from the follicular lymphomas by magnified features, it was easily diagnosed based on the macroscopic morphology. In conclusion, magnified endoscopic features, in combination with macroscopic features, are useful for differentiating follicular lymphomas from other duodenal diseases presenting whitish lesions.

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  • Interleukin-1 loop model for pathogenesis of Langerhans cell histiocytosis

    Ichiro Murakami, Michiko Matsushita, Takeshi Iwasaki, Satoshi Kuwamoto, Masako Kato, Keiko Nagata, Yasushi Horie, Kazuhiko Hayashi, Toshihiko Imamura, Akira Morimoto, Shinsaku Imashuku, Jean Gogusev, Francis Jaubert, Katsuyoshi Takata, Takashi Oka, Tadashi Yoshino

    CELL COMMUNICATION AND SIGNALING   13 ( 1 )   13 - 13   2015.2

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    We propose Langerhans cell histiocytosis (LCH) is an inflammatory process that is prolonged by mutations. We hypothesize that Merkel cell polyomavirus (MCPyV) infection triggers an interleukin-1 (IL-1) activation loop that underlies the pathogenesis of LCH. Langerhans cells (LCs) are antigen presenting cells in the skin. When LCs encounter exogenous antigens, they migrate from the epidermis into draining lymphoid tissues to initiate T-cell activity. It has been proposed that LC migration-related factors, including E-cadherin, matrix metalloproteinase, and Notch ligand induce LCH activity. We found that the tyrosine phosphatase SHP-1, which binds IL-1 receptor-associated kinase 1, is expressed at a significantly higher level in LCH affecting multiple organ systems (MS-LCH) than in LCH affecting a single organ system (SS-LCH). IL-1 stimulates T helper 17 cells and their signature cytokine IL-17 had been a matter of controversy. We detected higher levels of IL-17A receptor expression in MS-LCH than in SS-LCH and proposed an IL-17 endocrine model that could settle the controversy. IL-1 is the first cytokine secreted in response to sensitizers and promotes LC migration from sentinel tissues. Myeloid differentiation primary response 88 (MyD88), downstream of the IL-1 receptor, has functions in both RAS signaling and inflammation, leading to human cell transformation. In 2010, an activating mutation in the B-rapidly accelerated fibrosarcoma gene (BRAF) V600E was found in LCH. This BRAF mutation induces phosphorylation of the extracellular signal-regulated kinase (ERK) that may play an important role with MyD88 in LCH pathogenesis. However, phosphorylated ERK (pERK) is rapidly dephosphorylated by dual specificity phosphatase 6 (DUSP6), and limited proliferation is predicted in BRAF mutant cells. MyD88 binds pERK via its D-domain, thereby preventing pERK-DUSP6 interaction and maintaining ERK in an active, phosphorylated state. We detected MCPyV-DNA in the peripheral blood cells of two out of three patients with LCH in high-risk organs but not in those of patients with LCH in non-high-risk organs (0/12; P = .029). MCPyV infection can trigger precursor LCH cells with BRAF mutation to produce IL-1; the IL-1 loop is amplified in all LCH subclasses. Our model indicates both BRAF mutation and IL-1 loop regulation as potential therapeutic targets.

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  • Establishment of a Langerhans cell histiocytosis lesion cell line with dermal dendritic cell characteristics

    Ichiro Murakami, Jean Gogusev, Francis Jaubert, Michiko Matsushita, Kazuhiko Hayashi, Ikuo Miura, Takehiro Tanaka, Takashi Oka, Tadashi Yoshino

    ONCOLOGY REPORTS   33 ( 1 )   171 - 178   2015.1

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    A cell line named PRU-1, derived from a Langerhans cell (LC) histiocytosis (LCH) skull lesion of a 7-year-old boy, was established and characterized. PRU-1 is an adherent spindle-shaped cell line that shows no Birbeck granules on electron microscopy. Flow cytometric analysis of cells collected from the early seventh passage showed no LC phenotypes of CD1a and S100 protein. Immunostaining of PRU-1 cells also revealed no expression of LC markers but showed expression of CD11c, CD54 (ICAM-1) and CD68, which was also observed in some peripherally located cells of the original LCH lesion. The PRU-1 cells stained positive for factor XIIIa and negative for CD34, suggesting a dermal dendritic cell phenotype. Cytogenetic analyses revealed abnormalities such as 39, XY, -2, -4, -8, -12, -12, -14, add (18)(q21), 20, +mar and 44, XY, -11, -14, add(18)(q21). TCR rearrangement in the PRU-1 cells was not amplified by PCR. Tumorigenicity was not proven by xenografting into SCID mice. A conditioned medium from PRU-1 culture induced the proliferation of peripheral blood lymphocytes as well as the activation of monocytes from a healthy donor into CD1a-positive LC-like cells. Because the phenotypic characteristics of PRU-1 differed from those of CD1a-positive abnormal LC-like cells (LCH cells), it was likely that the PRU-1 cells were derived from peripherally located cells of the LCH lesion rather than LCH cells. LCH has been regarded as a type of granulomatous neoplasm with several intermingled inflammatory cells and influenced by stimuli such as Merkel cell polyomavirus (MCPyV) infection or cigarette smoking. However, in the PRU-1 cells, MCPyV-DNA was not detected by PCR. Stromal cell-like PRU-1 cells are likely to produce some growth or differentiation factors, which may play important roles in LCH lesion formation, cell maintenance and LC-like cell induction.

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

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

    SCIENTIFIC REPORTS   5   7696 - 7696   2015.1

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    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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  • Magnifying Endoscopic Observation of Duodenal Involvement of Follicular Lymphoma before and after Chemotherapy

    Masaya Iwamuro, Hiroyuki Okada, Katsuyoshi Takata, Nobuharu Fujii, Seiji Kawano, Yoshiro Kawahara, Tadashi Yoshino, Kazuhide Yamamoto

    INTERNAL MEDICINE   54 ( 14 )   1741 - 1745   2015

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    A 60-year-old Japanese man was diagnosed with systemic follicular lymphoma with duodenal, jejunal, and ileal involvement. The duodenal lesion showed typical endoscopic features with multiple whitish granules. Chemotherapy with bendamustine and rituximab was administered, and complete remission was confirmed by CT scanning and positron emission tomography scanning. Although the duodenal granular lesions did not completely disappear, magnifying observation for the remaining lesions showed no evidence of residual lymphoma. Complete remission was pathologically confirmed by biopsy examinations. This case suggests the usefulness of magnifying observation in evaluating the effects of treatment for duodenal follicular lymphoma lesions.

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  • Recurrence after Radiotherapy for Gastric Mucosa-associated Lymphoid Tissue (MALT) Lymphoma with Trisomy 18

    Hisashi Ishikawa, Masaya Iwamuro, Hiroyuki Okada, Keisuke Hori, Masahide Kita, Seiji Kawano, Yoshiro Kawahara, Takehiro Tanaka, Eisei Kondo, Tadashi Yoshino, Kazuhide Yamamoto

    INTERNAL MEDICINE   54 ( 8 )   911 - 916   2015

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    A 36-year-old Japanese woman presented with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the stomach. The gastric lesions only partially improved after eradication therapy for Helicobacter pylori. A fluorescence in situ hybridization analysis revealed no fusion genes of API2-MALT1, although trisomy of chromosome 18 was identified. Radiation therapy was initiated to treat the gastric lymphoma lesions, resulting in complete remission. However, MALT lymphoma recurred in the stomach 16 months later. This case indicates that intensive follow-up is required for MALT lymphoma associated with chromosomal aberrations in order to detect early relapse.

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  • 濾胞性リンパ腫のhistologic gradinigと特殊型、in situ病変認識の意義

    高田尚良, 吉野 正

    血液内科   70   14 - 20   2015

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  • 皮膚原発NK/T細胞リンパ腫の臨床病理学的特徴

    高田尚良, 吉野 正

    血液内科   70 ( 4 )   516 - 520   2015

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  • リンパ腫の分類と診断

    吉野 正

    リンパ学   38 ( 1 )   94 - 97   2015

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  • Lymphocyte-Rich Classical Hodgkin Lymphoma.

    Sakai J, Tanae K, Takahashi N, Nagata K, Yoshino T, Tamaru J, Niitsu N

    J Clin Exp Hematop.   55 ( 1 )   23 - 28   2015

  • 濾胞性リンパ腫の治療方針

    田利 晶, 麻奥英毅, 高田尚良, 藤森俊二, 田中信治, 藤原 恵, 吉野 正

    消化器内視鏡   27 ( 5 )   812 - 819   2015

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  • 2008年WHO分類の変更点と最近のTopics

    大西信彦, 吉野, 正

    消化器内視鏡   27 ( 5 )   740 - 747   2015

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  • リンパ節におけるIgG4関連疾患

    佐藤康晴, 吉野 正

    Modern Physician   35 ( 11 )   1351 - 1353   2015

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  • 濾胞性リンパ腫

    高田尚良, 吉野 正

    病理と臨床   33 ( 5 )   468 - 475   2015

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

    Junichi Kitagawa, Naoe Goto, Yuhei Shibata, Nobuhiko Nakamura, Hiroshi Nakamura, Nobuhiro Kanemura, Takeshi Hara, Katsuyoshi Takata, Yasuharu Sato, Tadashi Yoshino, Hisashi Tsurumi

    JOURNAL OF CLINICAL AND EXPERIMENTAL HEMATOPATHOLOGY   55 ( 3 )   169 - 174   2015

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    Concurrent seminoma andm alignant lymphoma of the testis is rare. We present a case of concurrent seminoma and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) in a 54-year-oldm an who complainedof painless left testicular enlargement. Radical left orchiectomy was performed. Macroscopically, the tumor (4.0 x 3.0 cm) was creamy, soft, and homogeneous, and microscopic evaluation revealed an alveolar structure of large cells that formeds heets, as well as colonization by other abnormal cells in a 1.0 x 1.0 cm area. The portion of the tumor comprising large abnormal cells was diagnosed as a seminoma, which was positive for c-kit by immunohistochemistry; the other portion was diagnosed as CD3/CD8, TIA, and granzyme B-positive PTCL-NOS. These two portions were clearly differentiated from one another. The patient received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy and a chieved complete response for 50 months. To our knowledge, this is the first reportedcase of synchronous advanced seminoma and PTCL.

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  • 血液病理学におけるIgG4関連疾患

    佐藤康晴, 吉野 正

    病理と臨床   33 ( 5 )   517 - 521   2015

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  • ICU管理が必要であったMulticentric Castleman Disease(MCD)/TAFRO症候群(1)

    近藤 英生, 佐藤 康晴, 浅野 豪, 花山 宜久, 木村 耕介, 塚原 紘平, 鵜川 豊世武, 谷本 光音, 吉野 正, 大塚 文男

    日本リンパ網内系学会会誌   55115   2015

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  • CNS浸潤伴う治療抵抗性ALK陽性ALCLに対しCrizotinibを使用した1例

    濱崎 豊, 石川 立則, 近藤 英生, 吉野 正, 長谷川 詠子, 瀬崎 伸夫, 藤原 英晃, 西森 久和, 松岡 賢市, 藤井 伸治, 前田 嘉信, 谷本 光音

    臨床血液   56 ( 5 )   2015

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  • Immunoglobulin Expressions Are Only Associated With MCPyV-positive Merkel Cell Carcinomas But Not With MCPyV-negative Ones Comparison of Prognosis

    Ichiro Murakami, Katsuyoshi Takata, Michiko Matsushita, Daisuke Nonaka, Takeshi Iwasaki, Satoshi Kuwamoto, Masako Kato, Takashi Mohri, Keiko Nagata, Yukisato Kitamura, Tadashi Yoshino, Kazuhiko Hayashi

    AMERICAN JOURNAL OF SURGICAL PATHOLOGY   38 ( 12 )   1627 - 1635   2014.12

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    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer, often associated with Merkel cell polyomavirus (MCPyV). Recently, immunoglobulin (Ig) expression was reported in MCC, thereby suggesting that B cells might be their cellular ancestors. We tested 30 MCCs (20 MCPyV-positive and 10 MCPyV-negative) using immunohistochemistry for the expressions of IgG, IgA, IgM, Ig kappa, Ig lambda, terminal desoxynucleotidyl transferase, paired box gene 5 (PAX5), octamer transcription factor-2 (Oct-2), and sex-determining region Y-box 11 (SOX11). We performed in situ hybridization for Ig kappa-mRNA or Ig lambda-mRNA and Ig heavy chain (IgH) gene rearrangement (IgH-R) analyses. The expressions of PAX5, TdT, Oct-2, and SOX11 were not significantly different between MCPyV-positive and MCPyV-negative MCCs. At least 1 of IgG, IgA, IgM, or Ig kappa was expressed in MCPyV-positive (14/20, 70%) and none in MCPyV-negative MCCs (P = 0.0003). There was a higher tendency for Ig kappa-mRNA expression (7/19, using in situ hybridization) and IgH-R (10/20, using polymerase chain reaction) in MCPyV-positive than in MCPyV-negative MCCs (0/10 and 2/10, respectively), thus suggesting a different Ig production pattern and pathogenesis between the 2 types of MCC. Ig expression or IgH-R in MCPyV-positive MCCs might be associated with MCPyV gene integration or expression in cancer cells but do not necessarily suggest a B-cell origin for MCCs. IgH expression or IgH-R nonsignificantly correlated with improved prognosis. However, these might be important factors that influence the survival of neoplastic cells and might allow the development of novel therapies for patients with MCPyV-positive MCCs.

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  • Prognostic biomarkers in patients with localized natural killer/T-cell lymphoma treated with concurrent chemoradiotherapy

    Motoko Yamaguchi, Katsuyoshi Takata, Tadashi Yoshino, Naoki Ishizuka, Masahiko Oguchi, Yukio Kobayashi, Yasushi Isobe, Kenichi Ishizawa, Nobuko Kubota, Kuniaki Itoh, Noriko Usui, Kana Miyazaki, Izumi Wasada, Shigeo Nakamura, Yoshihiro Matsuno, Kazuo Oshimi, Tomohiro Kinoshita, Kunihiro Tsukasaki, Kensei Tobinai

    CANCER SCIENCE   105 ( 11 )   1435 - 1441   2014.11

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    Concurrent chemoradiotherapy has become one of the standard management approaches for newly diagnosed localized nasal natural killer (NK)/T-cell lymphoma (NKTCL). Few data are available on the prognostic biomarkers of NKTCL among patients treated with concurrent chemoradiotherapy. To evaluate the prognostic significance of immunophenotypic biomarkers for patients treated with concurrent chemoradiotherapy, latent membrane protein 1 (LMP1), cutaneous lymphocyte antigen (CLA) and cell origin were examined in samples from 32 patients who were enrolled in the Japan Clinical Oncology Group 0211 trial and treated with concurrent chemoradiotherapy. LMP1 and CLA were positive in 66% (19/29) and 29% (9/31) of the cases examined, respectively. The median follow-up duration was 68months (range, 61-94). The patients with LMP1-positive tumors showed a better overall survival (OS) than the patients with LMP1-negative tumors (hazard ratio, 0.240; 95% confidence interval [CI], 0.057-1.013; 80% CI, 0.093-0.615; P=0.035). All five patients with LMP1-negative tumors who experienced disease progression died of lymphoma, and both patients with local failure had LMP1-negative tumors. There was no significant difference in OS according to CLA expression. A total of 27 (84%) cases were of NK-cell origin, two were of T-cell origin and three were of T-cell origin. In contrast to those with tumors of NK-cell origin, all five patients with NKTCL of T-cell origin were alive without relapse at the last follow up. Our results indicate that LMP1 expression is a favorable prognostic marker and suggest that a T-cell origin of the tumor may be a favorable prognostic marker for patients with localized NKTCL treated with concurrent chemoradiotherapy.

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  • Severe liver injury associated with simeprevir plus pegylated interferon/ribavirin therapy in a patient with treatment-naïve genotype 1b hepatitis C virus: a case report

    Takuro Igawa, Soichiro Fushimi, Ryuichi Matsuo, Fusao Ikeda, Kazuhiro Nouso, Tadashi Yoshino, Harushige Nakatsukasa

    Clinical Journal of Gastroenterology   7 ( 5 )   465 - 470   2014.10

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    A second-generation direct-acting antiviral agent, simeprevir, now provides a new treatment option for hepatitis C virus (HCV) infection with good safety profile in combination with pegylated interferon and ribavirin. We herein report a rare case of severe liver injury under simeprevir plus pegylated interferon/ribavirin therapy. We initiated this therapy in a 65-year-old male with treatment-naïve genotype 1b HCV. On day 28, the patient’s HCV-RNA was successfully eliminated, and his liver function was fully restored. However, on day 49, the serum alanine aminotransferase level was elevated at 700 IU/L. The HCV-RNA titer was still undetectable and the involvement of other possible viruses was negligible. A liver biopsy performed on day 60 showed an acute hepatitis pattern. The discontinuation of therapy alone successfully improved his liver damage on day 84. No other treatments such as steroids were required. According to the diagnostic criteria for drug-induced liver injury in Japan (DDW-J2004), the liver injury observed in this case can be associated with the administration of simeprevir plus pegylated interferon/ribavirin therapy. In conclusion, simeprevir plus pegylated interferon/ribavirin should be used with caution, as these agents may cause unreported serious adverse events including severe liver injury, despite their clinical safety profile.

    DOI: 10.1007/s12328-014-0527-x

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

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

    PATHOLOGY INTERNATIONAL   64 ( 10 )   527 - 532   2014.10

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    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.

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

    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   2014.10

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    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.

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  • EBV-POSITIVE MUCOCUTANEOUS ULCER ARISING IN A PATIENT WITH POLYCYTHEMIA VERA TREATED WITH ORAL HYDROXYUREA

    Toshihisa Hamada, Mariko Takao, Yoshinobu Maeda, Tadashi Yoshino, Yumi Aoyama, Keiji Iwatsuki

    JOURNAL OF DERMATOLOGY   41   41 - 41   2014.10

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  • Detection of T-cell receptor gamma gene rearrangement in paraffin-embedded T or natural killer/T-cell lymphoma samples using the BIOMED-2 protocol

    Tomoko Miyata-Takata, Katsuyoshi Takata, Sachiko Yamanouchi, Yasuharu Sato, Mai Harada, Takashi Oka, Takehiro Tanaka, Yoshinobu Maeda, Mitsune Tanimoto, Tadashi Yoshino

    LEUKEMIA & LYMPHOMA   55 ( 9 )   2161 - 2164   2014.9

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    While the use of polymerase chain reaction (PCR)-based clonality analysis of formalin-fixed paraffin-embedded (FFPE) tissue has recently become widespread, the detection sensitivity for lymphoma subtypes using FFPE samples is not well known. Here, we analyzed T-cell receptor gamma chain (TCRG) gene rearrangement clonality in 100 cases of T-or natural killer (NK)/T-cell lymphoma and examined detection sensitivity according to lymphoma subtype. Clonality was detected in approximately 80% of the major T-cell lymphoma subtypes: peripheral T-cell lymphoma, not otherwise specified, 84% (21/25 cases); angioimmunoblastic T-cell lymphoma, 71% (15/21 cases); and adult T-cell leukemia/lymphoma, 80% (8/10 cases). The number of clonal peaks differed according to subtype. TCRG gene rearrangement was not detected in 63 cases of B-cell lymphoma or reactive lesions. Thus, clonality analysis can effectively and reliably detect TCRG gene rearrangement in T-cell lymphoma cases and could, therefore, be a useful diagnostic tool in routine practice.

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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   2014.8

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    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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  • 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   2014.8

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    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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  • 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   2014.8

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    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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  • 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   2014.7

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    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.

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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   2014.7

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    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   2014.7

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    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.

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  • IgG4関連疾患におけるEpstein‐Barr virus(EBV)感染細胞の検討

    TAKEUCHI MAI, SATO YASUHARU, YASUI HIROSHI, OZAWA HIROAKI, ONO KYOTARO, TAKATA KATSUYOSHI, ASANO NAOKO, NAKAMURA SHIGEO, YOSHINO TADASHI

    日本リンパ網内系学会会誌   54   114   2014.6

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    J-GLOBAL

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  • Type AB thymoma is not a mixed tumor of type A and type B thymomas, but a distinct type of thymoma

    Yukari Miki, Kana Hamada, Tadashi Yoshino, Katsuya Miyatani, Kiyoshi Takahashi

    VIRCHOWS ARCHIV   464 ( 6 )   725 - 734   2014.6

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    Type AB thymoma is generally regarded to be a mixture of type A and type B thymomas, but has not been studied extensively. In this study, we precisely investigated the characteristics of type AB thymoma immunohistochemically and compared it with other types of thymoma, including type A, metaplastic, and type B1 thymoma. In type A thymoma, the tumor cells were composed solely of pan-cytokeratin (CKAE1/AE3)(+) claudin-1(+) vimentin(-) epithelial membrane antigen (EMA)-short spindle cells. Metaplastic thymoma exhibited biphasic architecture of epithelial islands of short spindle cells, which were phenotypically almost identical to the tumor cells in type A thymoma, and anastomosing bundles of CK-AE1/AE3(-) claudin-1(-) vimentin(+) EMA(+) fibroblast-like long spindle-shaped epithelial cells. Interestingly, we found that there were two distinctive subtypes of cell in type AB thymoma: the conventional subtype and the metaplastic subtype. The conventional subtype is characterized by type A-like components resembling type A thymoma. The metaplastic subtype is characterized by type A-like components extensively resembling the anastomosing bundles of fibroblast-like long spindle epithelial cells. Interestingly, the metaplastic subtype was a major subtype (14/19 cases), while the conventional subtype was a minor one (5/19 cases). In contrast to the rarity of metaplastic thymoma, the metaplastic subtype of type AB thymoma appears to be a major subtype of type AB thymoma.

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  • 治療抵抗性DLBCLの自己末梢血幹細胞移植併用大量化学療法(HDT/ASCT)後の再発に対しHLA半合致同種造血幹細胞移植(haploHSCT)を行い完全寛解となった一例

    塩手 康弘, 近藤 英生, 石川 立則, 佐伯 恭昌, 谷 勝真, 山本 宜和, 松岡 賢市, 西森 久和, 藤井 伸治, 前田 嘉信, 谷本 光音, 吉野 正

    日本リンパ網内系学会会誌   54   122 - 122   2014.6

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  • High viral load of Merkel cell polyomavirus DNA sequences in Langerhans cell sarcoma tissues

    Ichiro Murakami, Michiko Matsushita, Takeshi Iwasaki, Satoshi Kuwamoto, Masako Kato, Yasushi Horie, Kazuhiko Hayashi, Jean Gogusev, Francis Jaubert, Shu Nakamoto, Mitsunori Yamakawa, Hirokazu Nakamine, Katsuyoshi Takata, Takashi Oka, Tadashi Yoshino

    INFECTIOUS AGENTS AND CANCER   9   15 - 15   2014.5

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    Background: Langerhans cell (LC) sarcoma (LCS) is a high-grade neoplasm with overtly malignant cytologic features and an LC phenotype. We very recently suggested that LC behaves as a reservoir for common dermotropic Merkel cell polyomavirus (MCPyV) and determined the relationship between LC histiocytosis (LCH), which has an underlining oncogenic capacity, and MCPyV as a trigger for a reactive process rather than a neoplastic process. We propose LC to be a reservoir for MCPyV and hypothesize that some LCS subtypes may be related to the MCPyV agent.
    Findings: We examined seven LCS tissues using multiplex quantitative PCR (Q-PCR) and immunohistochemistry with anti MCPyV large-T (LT) antigen antibody. High viral loads of MCPyV DNA sequences (viral load = relative levels of MCPyV) were detected (0.328-0.772 copies/cell (Merkel cell carcinoma (MCC) = 1.0)) using Q-PCR in 43% (3/7) tissues, but LT antigen expression was not observed (0/7).
    Conclusions: Frequent MCPyV-DNA amplification suggests that LCS in some patients may be related to MCPyV infection. Moreover, the higher viral load of LCS (median, 0.453 copies/cell) than low load of LCH (0.003, median of 12 cases) (P &lt; 0.01) may suggest a virally induced tumorigenic process in some LCS. Although the absence of LT antigen expression may indicate a different role for MCPyV in this pathology, some subtypes of LCS may develop in the background of MCPyV-infected LC. To the best of our knowledge, this is the first report on the relationship between MCPyV and LCS. The recent discovery of MCPyV opened new therapeutic avenues for MCC. These data open novel possibilities for therapeutic interventions against LCS.

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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   2014.5

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    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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  • 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   2014.4

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    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

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  • Diagnostic accuracy of endoscopic biopsies for the diagnosis of gastrointestinal follicular lymphoma: a clinicopathologic study of 48 patients

    Masaya Iwamuro, Hiroyuki Okada, Katsuyoshi Takata, Soichiro Nose, Katsuya Miyatani, Tadashi Yoshino, Kazuhide Yamamoto

    ANNALS OF DIAGNOSTIC PATHOLOGY   18 ( 2 )   99 - 103   2014.4

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    The purpose of this study was to reveal the diagnostic accuracy of initial pathologic assessment of biopsied samples in patients with gastrointestinal follicular lymphoma lesions. A total of 48 patients with follicular lymphoma (Lugano system stage I: n = 30; II1: n = 4; II2: n = 4; IV: n = 10) with gastrointestinal involvement who underwent endoscopic biopsy were enrolled and retrospectively reviewed. Nine (18.8%) of the 48 patients were not appropriately diagnosed as having follicular lymphoma at the initial biopsy. The initial pathological diagnosis included extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (n = 4), necrotic tissue (n = 2), duodenitis (n = 1), or suspected lymphoma of unspecified subtype (n = 2). The reasons for these inappropriate diagnoses were insufficient histopathologic analysis lacking CD10 and BCL2 staining (n = 7) and unsuitable biopsy samples taken from erosions or ulcers that contained scanty lymphoma cells or no lymphoid follicles (n = 2). In conclusion, incomplete histopathologic analysis and unsuitable biopsy samples are pitfalls in the diagnosis of gastrointestinal follicular lymphoma. (c) 2014 Elsevier Inc. All rights reserved.

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  • Elevated soluble IL-2 receptor levels correlate with tumor bulk of follicular lymphomas with intestinal involvement

    Masaya Iwamuro, Katsuji Shinagawa, Hiroyuki Okada, Katsuyoshi Takata, Tadashi Yoshino, Kazuhide Yamamoto

    CLINICAL BIOCHEMISTRY   47 ( 3 )   191 - 195   2014.2

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    Objectives: Establish a correlation between serum soluble interleukin 2 receptor (sIL-2R) levels and clinical characteristics of follicular lymphoma patients with gastrointestinal involvement.
    Design and methods: Patients (n = 44) presenting with follicular lymphoma lesions in the gastrointestinal tract were enrolled into the study and divided into 2 groups based on sIL-2R levels (normal vs. elevated). Clinical characteristics were also analyzed between groups.
    Results: Patients with elevated sIL-2R levels likely had systemic follicular lymphoma involvement (Ann Arbor system staging IIIES/IV or Lugano system staging II-2/IV), involvement of 5 or more nodal areas, and presentation of bulky tumors in the gastrointestinal tract. These patients also presented a high Follicular Lymphoma International Prognostic Index (FLIPI) score, suggestive of poor prognosis. No differences were found among other clinical characteristics including sex, age at lymphoma diagnosis, histological grade, LDH levels, bone marrow involvement, hemoglobin levels, and identification of tracer accumulation in gastrointestinal lesions by positron-emission tomography scanning.
    Conclusions: sIL-2R levels can be used as an independent prognostic index in follicular lymphoma patients based on the correlation with the FLIPI score. Moreover, since high sIL-2R levels were associated with a large tumor bulk, sIL-2R may serve as a good indicator for monitoring disease relapse or progression. (C) 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

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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 - 41   2014.2

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    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.

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

    Katsuyoshi Takata, Motohiko Tanino, Daisuke Ennishi, 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   608 - 615   2014.1

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    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 gene

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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   2014.1

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    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.

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  • Merkel cell polyomavirus DNA sequences in peripheral blood and tissues from patients with Langerhans cell histiocytosis

    Ichiro Murakami, Michiko Matsushita, Takeshi Iwasaki, Satoshi Kuwamoto, Masako Kato, Yasushi Horie, Kazuhiko Hayashi, Toshihiko Imamura, Akira Morimoto, Shinsaku Imashuku, Jean Gogusev, Francis Jaubert, Katsuyoshi Takata, Takashi Oka, Tadashi Yoshino

    HUMAN PATHOLOGY   45 ( 1 )   119 - 126   2014.1

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    Langerhans cell histiocytosis (LCH) is a group of granulomatous disorders in which abnormal Langerhans cells proliferate as either a localized lesion in a single bone or disseminated disease involving two or more organs or systems. Because the different LCH forms exhibit significantly elevated levels of inflammatory molecules, including pro-inflammatory cytokines and tissue-degrading enzymes, we investigated for a possible viral trigger in LCH pathogenesis. We looked for Merkel cell polyomavirus (MCPyV) in peripheral blood cells and tissues using quantitative real-time PCR and immunohistochemistry staining with anti-MCPyV large T-antigen antibody. Our findings revealed elevated amounts of MCPyV DNA in the peripheral blood cells of 2 of 3 patients affected by LCH with high-risk organ involvement (RO+) and absence of MCPyV DNA in the blood cells in all 12 LCH-RO-patients (P = .029). With lower viral loads (0.002-0.033 copies/cell), an elevated number of MCPyV DNA sequences was detected in 12 LCH tissues in comparison with control tissues obtained from patients with reactive lymphoid hyperplasia (0/5; P = .0007), skin diseases not related to LCH in children younger than 2 years (0/11; P = .0007), or dermatopathic lymphadenopathy (5/20; P = .0002). The data, including frequent but lower viral loads and low large-T antigen expression rate (2/13 LCH tissues), suggest that development of LCH as a reactive rather than a neoplastic process may be related to MCPyV infection. (C) 2014 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.humpath.2013.05.028

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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   2014.1

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    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.

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  • Epstein-Barr virus-associated T/natural killer-cell lymphomas in the elderly: The first consensus meeting in Kofu 2013

    Toshihisa Hamada, Shigeo Nakamura, Young-Hyeh Ko, Tadashi Yoshino, Koichi Ohshima, Takamitsu Matsuzawa, Keiko Miura, Toshifumi Takahashi, Hisashi Nomura, Tomomi Hoshino, Daisuke Suzuki, Shinji Shimada, Keiji Iwatsuki

    JOURNAL OF DERMATOLOGY   41 ( 1 )   40 - 42   2014.1

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    From a clinicopathological conference on nine elderly patients with Epstein-Barr virus (EBV)-associated T/natural killer (NK)-cell lymphoma, we have addressed the patients' backgrounds, clinical manifestations, histopathological findings, cytogenesis, complications and prognoses. Among these elderly patients (&gt;65years old), seven patients had extranodal NK/T-cell lymphoma, nasal type (ENKL) with an NK-cell phenotype, and two patients had EBV+ T-cell lymphomas or lymphoproliferative disorders (LPD) with cutaneous lesions mimicking pityriasis lichenoides et varioliformis acuta (PLEVA) or hydroa vacciniforme (HV). No patients had a previous episode of EBV-related symptoms such as infectious mononucleosis, chronic active EBV infection, HV or hypersensitivity to mosquito bites. Elderly patients with ENKL may show the centroblastoid variant. EBV(+)CD8(+)CD56(+/-) lymphocytes may be responsible for the development of PLEVA or HV-like cutaneous lesions in the elderly.

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  • 濾胞性リンパ腫とマントル細胞リンパ腫の病理

    高田尚良, 岡田裕之, 岩室雅也, 田利 晶, 吉野 正

    胃と腸   49 ( 5 )   649 - 655   2014

  • 濾胞性リンパ腫の診断と治療

    田利 晶, 麻奥英毅, 藤原 恵, 吉野 正, 藤森俊二, 田中信治

    胃と腸   49 ( 5 )   664 - 674   2014

  • Rapidly progressed primary intestinal follicular lymphoma with elevation of soluble interleukin-2 receptor levels.

    Iwamuro M, Takenaka R, Mori A, Fujiki S, Miyake T, Asakura S, Okada H, Takata K, Yoshino T, Yamamoto K

    Case Rep Oncol Med.   2014   ID:59248   2014

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  • In situ follicular lymphomaとは何か

    原田 舞, 吉野 正

    血液内科   68 ( 1 )   129 - 133   2014

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  • リンパ腫のWHO分類と病型頻度

    竹内真衣, 佐藤康晴, 吉野 正

    日本臨床   72 ( 3 )   436 - 440   2014

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  • Regression of Duodenal Follicular Lymphoma: Susceptible to H-pylori Eradication?

    Masaya Iwamuro, Hiroyuki Okada, Katsuji Shinagawa, Katsuyoshi Takata, Tadashi Yoshino, Kazuhide Yamamoto

    INTERNAL MEDICINE   53 ( 12 )   1397 - 1397   2014

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    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)   Publisher:JAPAN SOC INTERNAL MEDICINE  

    DOI: 10.2169/internalmedicine.53.2433

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  • Primary Cutaneous NK/T-cell Lymphoma, Nasal Type and CD56-positive Peripheral T-cell Lymphoma: A Cellular Lineage and Clinicopathologic Study of 60 Patients From Asia.

    Takata K, Hong ME, Sitthinamsuwan P, Loong F, Tan SY, Liau JY, Hsieh PP, Ng SB, Yang SF, Pongpruttipan T, Sukpanichnant S, Kwong YL, Hyeh Ko Y, Cho YT, Chng WJ, Matsushita T, Yoshino T, Chuang SS

    Am J Surg Pathol.   39 ( 1 )   1 - 12   2014

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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

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    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

    J Clin Exp Hematop   54 ( 1 )   3 - 9   2014

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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   2013.12

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    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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  • 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   2013.12

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    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.

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  • In aggressive variants of non-Hodgkin lymphomas, Ezh2 is strongly expressed and polycomb repressive complex PRC1.4 dominates over PRC1.2

    Lamia Abd Al Kader, Takashi Oka, Katsuyoshi Takata, Xu Sun, Hiaki Sato, Ichiro Murakami, Tomohiro Toji, Akihiro Manabe, Hiroshi Kimura, Tadashi Yoshino

    VIRCHOWS ARCHIV   463 ( 5 )   697 - 711   2013.11

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    Polycomb group (PcG) proteins are important for the regulation of hematopoiesis by regulating chromatin compaction and silencing genes related to differentiation and cell cycle. Overexpression of enhancer of zeste homologue 2 (Ezh2) and Bmi-1/PCGF4 has been implicated in solid organ cancers, while Mel-18/PCGF2 has been reported as a tumor suppressor. Detailed expression profiles of PcG proteins and their diagnostic significance in malignant lymphomas are still unknown. In this study, we analyzed the expression levels of Ezh2, Bmi-1, Mel-18, and Ki67 in 197 Hodgkin's and non-Hodgkin's lymphoma patient samples and in lymphoma cell lines using immunohistochemistry, fluorescent immunocytochemistry, and Western blotting. Immunohistochemical staining showed that Ezh2 expression was significantly increased in aggressive compared to indolent subtypes of B cell neoplasms (P = 0.000-0.030), while no significant differences in Bmi-1 expression were found between these subtypes. Compared to the normal counterpart, T cell lymphomas showed significant overexpression of Bmi-1 (P = 0.011) and Ezh2 (P = 0.000). The Ki67 labeling index showed a positive correlation with Ezh2 expression in B cell lymphomas (correlation coefficient (Co) = 0.983, P = 0.000) and T/NK cell lymphomas (Co = 0.629, P = 0.000). Fluorescent immunohistochemical staining showed coexpression of Ezh2 and Ki67 in the same tumor cells, indicating that Ezh2 expression correlates with cell proliferation. Both B and T/NK cell neoplasms showed low expression of Mel-18 and high expression of both Bmi-1 and Ezh2. In conclusion, in aggressive lymphoma variants, Ezh2 is strongly expressed and polycomb repressive complex PRC1.4 dominates over PRC1.2. Coexpression of Bmi-1 and Ezh2 is a characteristic of aggressive lymphomas. Ezh2 correlates with the proliferation and aggressive nature of non-Hodgkin's lymphomas.

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  • In aggressive variants of non-Hodgkin lymphomas, Ezh2 is strongly expressed and polycomb repressive complex PRC1.4 dominates over PRC1.2

    Lamia Abd Al Kader, Takashi Oka, Katsuyoshi Takata, Xu Sun, Hiaki Sato, Ichiro Murakami, Tomohiro Toji, Akihiro Manabe, Hiroshi Kimura, Tadashi Yoshino

    VIRCHOWS ARCHIV   463 ( 5 )   697 - 711   2013.11

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    Polycomb group (PcG) proteins are important for the regulation of hematopoiesis by regulating chromatin compaction and silencing genes related to differentiation and cell cycle. Overexpression of enhancer of zeste homologue 2 (Ezh2) and Bmi-1/PCGF4 has been implicated in solid organ cancers, while Mel-18/PCGF2 has been reported as a tumor suppressor. Detailed expression profiles of PcG proteins and their diagnostic significance in malignant lymphomas are still unknown. In this study, we analyzed the expression levels of Ezh2, Bmi-1, Mel-18, and Ki67 in 197 Hodgkin's and non-Hodgkin's lymphoma patient samples and in lymphoma cell lines using immunohistochemistry, fluorescent immunocytochemistry, and Western blotting. Immunohistochemical staining showed that Ezh2 expression was significantly increased in aggressive compared to indolent subtypes of B cell neoplasms (P = 0.000-0.030), while no significant differences in Bmi-1 expression were found between these subtypes. Compared to the normal counterpart, T cell lymphomas showed significant overexpression of Bmi-1 (P = 0.011) and Ezh2 (P = 0.000). The Ki67 labeling index showed a positive correlation with Ezh2 expression in B cell lymphomas (correlation coefficient (Co) = 0.983, P = 0.000) and T/NK cell lymphomas (Co = 0.629, P = 0.000). Fluorescent immunohistochemical staining showed coexpression of Ezh2 and Ki67 in the same tumor cells, indicating that Ezh2 expression correlates with cell proliferation. Both B and T/NK cell neoplasms showed low expression of Mel-18 and high expression of both Bmi-1 and Ezh2. In conclusion, in aggressive lymphoma variants, Ezh2 is strongly expressed and polycomb repressive complex PRC1.4 dominates over PRC1.2. Coexpression of Bmi-1 and Ezh2 is a characteristic of aggressive lymphomas. Ezh2 correlates with the proliferation and aggressive nature of non-Hodgkin's lymphomas.

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  • Pathogenic mechanisms of influenza A(H1N1)pdm09 infection elucidated on gene expression profiling

    Nobuko Yamashita, Hirokazu Tsukahara, Mitsuru Tsuge, Yoshiharu Nagaoka, Masato Yashiro, Yukie Saito, Yosuke Fujii, Takashi Oka, Tsuneo Morishima

    Pediatrics International   55 ( 5 )   572 - 577   2013.10

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    Background: The pathogenic mechanisms underlying influenza A(H1N1)pdm09-associated central nervous system (CNS) manifestations and pneumonia remain unclear. This study examined A(H1N1)pdm09 host responses using gene expression profiles of patients' peripheral blood. Methods: Sixteen A(H1N1)pdm09-infected children in three groups were examined: a CNS group, with convulsion and altered consciousness (n = 6)
    a pneumonia (Pneu) group (n = 5)
    and a group of infected control patients (n = 5). The signal ratios of the acute to recovery phases in CNS or Pneu were analyzed versus those of the control. Results: The CNS (619 transcripts) and Pneu (656 transcripts) groups had significantly increased signal ratios compared to the control group. Regarding the increased ratios of transcripts shown by multiple probes, contactin-associated protein-like 3 transcripts, oleoyl-ACP hydrolase transcripts, and interleukin 1 type 1 receptor were observed in CNS and Pneu. Increased ratios of prostaglandin-endoperoxide synthase 2 and α-synuclein were characteristic of CNS. Alkaline phosphatase and the Fc fragment of IgA receptor were characteristic of Pneu. Regarding enriched gene ontology terms, 'response to lipopolysaccharide', 'innate immune response', and 'intrinsic to membrane' were observed commonly in CNS and Pneu. Enriched gene ontology terms related to 'hemoglobin' and 'hemostasis' were, respectively, characteristic of CNS and Pneu. Conclusion: These symptom-associated transcripts might be some clues to the pathogenesis of the A(H1N1)pdm09 infection. © 2013 Japan Pediatric Society.

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  • Histamine inhibits high mobility group box 1-induced adhesion molecule expression on human monocytes

    Hideo Takahashi, Hiroshi Sadamori, Kiyoshi Teshigawara, Atsuko Niwa, Keyue Liu, Hidenori Wake, Shuji Mori, Tadashi Yoshino, Masahiro Nishibori

    EUROPEAN JOURNAL OF PHARMACOLOGY   718 ( 1-3 )   305 - 313   2013.10

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    Cell cell interaction through binding of adhesion molecules on monocytes Lo Lheir ligancls on T-cells plays roles in cyLokine production and lymphocyte proliferation. High mobility group box 1 (HMGB1), an abundant and conserved nuclear protein, acts in the extracellular environment as a primary pro inflammatory signal. HMGB1 induces expression of intercellular adhesion molecule (ICAM), 37.1, 37.2 and CD40 on rnonocytes, resulting in production of interferon (lFN)-7 and tumor necrosis factor (TNF)-u production and lymphocyte proliferation in human peripheral blood mononuclear cells (PBMCs). Histamine inhibits pro-inflammatory cytokine production via histamine H-2-receptors; however, it is not known whether histamine inhibits HMGB1 activity. This study was designed to study the inhibitory effect of histamine on HMGB1 activity. We examined the effect of histamine on HMGB1-induced expression of (ICAM), B7.1, B7.2 and CD40 on monocytes, production of IFN-gamma and TNF-alpha and lymphocyte proliferation in PBMCs. Histamine inhibited HMGB1 activity in a concentration-dependent manner. The effects of histamine were partially ablated by the H-2-receptor antagonist, famotidine, and mimicked by the H-2/H-4-receptor agonists, dimapriL and 4-methylhistamine. Histamine induced cyclic adenosine monophosphate (cAMP) production in the presence and absence of HMGB1. The effects of histamine were reversed by the protein kinase A (PKA) inhibitor, H89, and mimicked by the membrane-permeable cAMP analog, dibutyryl cAMP (dbcAMP), and the adenylate c-yclase activator, forskolin. These results together indicated that histamine inhibited HMGB1 activity (C) 2013 Elsevier B.V. All rights reserved

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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   2013.10

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    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.

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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   2013.9

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    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.

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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   2013.8

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    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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  • 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   2013.8

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    DOI: 10.1038/modpathol.2013.118

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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   2013.8

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  • Over-expression of BACH2 is related to ongoing somatic hypermutation of the immunoglobulin heavy chain gene variable region of de novo diffuse large B-cell lymphoma

    Tomoki Kikuchi, Mami Tokunaka, Yara Yukie Kikuti, Joaquim Carreras, Go Ogura, Susumu Takekoshi, Minoru Kojima, Kiyoshi Ando, Yuko Hashimoto, Masafumi Abe, Katsuyoshi Takata, Tadashi Yoshino, Akihiko Muto, Kazuhiko Igarashi, Naoya Nakamura

    Pathology International   63 ( 7 )   339 - 344   2013.7

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    The basic region-leucine zipper (bZip) factor BTB, CNC homology 2 (BACH2) is known to have important roles in class switch recombination and somatic hypermutation (SHM) of the immunoglobulin (Ig) gene. In this study, we investigated the relationship between the expression of BACH2 and the status of SHM of the Ig heavy chain gene variable region (IgHV) for SHM in diffuse large B-cell lymphoma (DLBCL). We examined 20 cases of DLBCL, 13 of which were germinal center B-cell (GCB) DLBCL and 7 were non-GCB DLBCL. Seven cases were negative, 6 were positive (cytoplasmic expression) and 7 were strongly positive (both nuclear and cytoplasmic expression) for BACH2. Confirmed mutation (CM) was identified in 8 cases and the CM index (number of confirmed mutations per 10 subclones) was distributed from 0 to 5. A CM index of 7 strongly positive (over-expression) cases with BACH2 were distributed from 0 to 5, and that of 7 negative and 6 positive cases were distributed from 0 to 1. Over-expression of BACH2 was statistically related to CM index (P = 0.008). In conclusion, over-expression of BACH2 is critical for ongoing SHM of IgHV in DLBCL, and our data suggest that BACH2 may play an essential role for SHM of the Ig gene in B-cell lymphoma. © 2013 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

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  • Comparison of outcomes between autologous and allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphomas with central review of pathology

    S-W Kim, S-S Yoon, R. Suzuki, Y. Matsuno, H. G. Yi, T. Yoshida, M. Imamura, A. Wake, K. Miura, M. Hino, T. Ishikawa, J. S. Kim, Y. Maeda, J-J Lee, H. J. Kang, H. S. Lee, J-H Lee, K. Izutsu, T. Fukuda, C. W. Kim, T. Yoshino, K. Ohshima, S. Nakamura, K. Nagafuji, J. Suzumiya, M. Harada, C. S. Kim

    LEUKEMIA   27 ( 6 )   1394 - 1397   2013.6

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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   2013.5

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    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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  • Stage I and II Follicular Lymphoma With Gastrointestinal Involvement: Long-Term Follow-up of No Initial Therapy

    Hiroyuki Okada, Katsuyoshi Takata, Yoshiro Kawahara, Junichiro Nasu, Seiji Kawano, Masahide Kita, Takao Tsuzuki, Minoru Matubara, Keisuke Hori, Hiromitu Kanzaki, Sayo Kobayashi, Tadashi Yoshino, Kazuhide Yamamoto

    GASTROENTEROLOGY   144 ( 5 )   S761 - S762   2013.5

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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

    ANDO MIDORI, SATO YASUHARU, TAKATA KATSUYOSHI, NOMOTO JUNKO, NAKAMURA SHIGEO, OSHIMA KOICHI, TAKEUCHI TAMOTSU, KOBAYASHI YUKIO, YOSHINO TADASHI

    日本病理学会会誌   102 ( 1 )   481 - 481   2013.4

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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   2013.4

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    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.

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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   2013.4

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  • Usefulness of positron emission tomography in primary intestinal follicular lymphoma

    Akira Tari, Hideki Asaoku, Masaki Kunihiro, Shinji Tanaka, Tadashi Yoshino

    WORLD JOURNAL OF GASTROENTEROLOGY   19 ( 12 )   1992 - 1996   2013.3

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    Double-balloon enteroscopy (DBE) and video capsule endoscopy are useful for the diagnosis of lymphoma in the small intestine. However, DBE cannot be safely performed in cases with passage disturbance due to wall thickening and stenosis. Additionally, video capsule endoscopy cannot be performed in such cases because of the risk of retention. Here, we report 4 cases of primary follicular lymphoma of the gastrointestinal tract that could be detected using F-18-fluorodeoxyglucose positron emission tomography combined with computed tomography (PET-CT). The endoscopic findings of these 4 cases included lesions with wall thickening, which comprised macroscopically clusters of nodules, dense clusters of whitish granules or small nodules, fold thickening and ulcers with irregular margins that occupied the whole lumen with edematous mucosa. All patients fulfilled the World Health Organization grade 1 criteria. F-18-fluorodeoxyglucose PET-CT can help predict the risks that may result from certain endoscopic examinations, such as DBE and video capsule endoscopy. (C) 2013 Baishideng. All rights reserved.

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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 )   2013.2

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    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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  • Role of cell-cell interactions in high mobility group box 1 cytokine activity in human peripheral blood mononuclear cells and mouse splenocytes

    Hideo Kohka Takahashi, Hiroshi Sadamori, Keyue Liu, Hidenori Wake, Shuji Mori, Tadashi Yoshino, Yasuhiko Yamamoto, Hiroshi Yamamoto, Masahiro Nishibori

    European Journal of Pharmacology   701 ( 1-3 )   194 - 202   2013.2

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    Cell-cell interaction through binding of intercellular adhesion molecule (ICAM), B7.1, B7.2 and CD40 on monocytes to their ligands on T-cells plays a number of roles in cytokine. High mobility group box 1 (HMGB1), an abundant and conserved nuclproduction and lymphocyte proliferationear protein, acts in the extracellular environment as a primary pro-inflammatory signal. The receptor for advanced glycation end products (RAGE), toll-like receptor (TLR)-2 and TLR-4 are receptors for HMGB1. HMGB1 induces pro-inflammatory cytokine production in monocytes and T-cells. This study was designed to study the cellular mechanism of cytokine production. HMGB1 concentration-dependently induced ICAM-1, B7.1, B7.2 and CD40 expression on monocytes, and interferon (IFN)-γ and tumor necrosis factor (TNF)-α production and lymphocyte proliferation in human peripheral blood mononuclear cells (PBMCs). These HMGB1 activities depended on the stimulation of RAGE on monocytes. HMGB1 also up-regulated RAGE, but not TLR-2 or TLR-4, expression on monocytes, which was inhibited by antibodies (Abs) against ICAM-1, B7.1, B7.2 and CD40. These results together indicated that HMGB1 could induce an intimate cellular interplay between monocytes and T-cells in PBMCs through the stimulation and up-regulation of RAGE and other adhesive molecules on monocytes. © 2012 Elsevier B.V. All rights reserved.

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  • Serologic Factors in Early Relapse of IgG4-Related Orbital Inflammation After Steroid Treatment

    Toshinobu Kubota, Masao Katayama, Suzuko Moritani, Tadashi Yoshino

    AMERICAN JOURNAL OF OPHTHALMOLOGY   155 ( 2 )   373 - 379   2013.2

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    PURPOSE: To determine whether serologic factors correlate with early relapse in cases of IgG4-related orbital inflammation, a lymphoproliferative disorder.
    DESIGN: Retrospective cohort study.
    METHODS: We examined the orbital images and serum data of 30 patients with (n = 24) or without (n = 6) corticosteroid treatment before and after corticosteroid treatment and 6 months after discontinuation of corticosteroid treatment.
    RESULTS: Seven patients (23%) (all with corticosteroid treatment) had elevated serum levels of rheumatoid factor. Of the 24 patients with corticosteroid treatment, 24 (100%) showed regression of the lesion, but 8 of the 24 (33%) showed relapse. The serum IgG4 levels before and after corticosteroid treatment were not significantly different between the relapsed and non-relapsed groups (P = .5 and P = .2, respectively). However, the incidence of patients who were rheumatoid factor positive was significantly higher in the relapsed group (P = .02). The 6 patients without corticosteroid treatment showed minor proliferation or regression of the lesion at the 6-month follow-up.
    CONCLUSIONS: The serum rheumatoid factor level may correlate with proliferative activity in IgG4-related orbital inflammation. (Am J Ophthalmol 2013;155: 373-379. (c) 2013 by Elsevier Inc. All rights reserved.)

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  • IL-17A receptor expression differs between subclasses of Langerhans cell histiocytosis, which might settle the IL-17A controversy

    Ichiro Murakami, Akira Morimoto, Takashi Oka, Satoshi Kuwamoto, Masako Kato, Yasushi Horie, Kazuhiko Hayashi, Jean Gogusev, Francis Jaubert, Shinsaku Imashuku, Lamia Abd Al-Kadar, Katsuyoshi Takata, Tadashi Yoshino

    VIRCHOWS ARCHIV   462 ( 2 )   219 - 228   2013.2

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    Langerhans cell histiocytosis (LCH) is a lymphoproliferative disorder consisting of abnormal Langerhans cell-like cells and other lymphoid cells. LCH presents as either a multisystem LCH (LCH-MS) or a single-system LCH (LCH-SS). Currently, neither the pathogeneses nor the factors that define these disease subclasses have been elucidated. The interleukin (IL)-17A autocrine LCH model and IL-17A-targeted therapies have been proposed and have engendered much controversy. Those authors showed high serum IL-17A levels in LCH and argued that serum IL-17A-dependent fusion activities in vitro, rather than serum IL-17A levels, correlated with LCH severity (i.e. the IL-17A paradox). In contrast, others could not confirm the IL-17A autocrine model. So began the controversy on IL-17A, which still continues. We approached the IL-17A controversy and the IL-17A paradox from a new perspective in considering the expression levels of IL-17A receptor (IL-17RA). We detected higher levels of IL-17RA protein expression in LCH-MS (n = 10) as compared to LCH-SS (n = 9) (P = 0.041) by immunofluorescence. We reconfirmed these data by re-analyzing GSE16395 mRNA data. We found that serum levels of IL-17A were higher in LCH (n = 38) as compared to controls (n = 20) (P = 0.005) with no significant difference between LCH subclasses. We propose an IL-17A endocrine model and stress that changes in IL-17RA expression levels are important for defining LCH subclasses. We hypothesize that these IL-17RA data could clarify the IL-17A controversy and the IL-17A paradox. As a potential treatment of LCH-MS, we indicate the possibility of an IL-17RA-targeted therapy.

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  • IL-17A receptor expression differs between subclasses of Langerhans cell histiocytosis, which might settle the IL-17A controversy

    Ichiro Murakami, Akira Morimoto, Takashi Oka, Satoshi Kuwamoto, Masako Kato, Yasushi Horie, Kazuhiko Hayashi, Jean Gogusev, Francis Jaubert, Shinsaku Imashuku, Lamia Abd Al-Kadar, Katsuyoshi Takata, Tadashi Yoshino

    VIRCHOWS ARCHIV   462 ( 2 )   219 - 228   2013.2

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    Langerhans cell histiocytosis (LCH) is a lymphoproliferative disorder consisting of abnormal Langerhans cell-like cells and other lymphoid cells. LCH presents as either a multisystem LCH (LCH-MS) or a single-system LCH (LCH-SS). Currently, neither the pathogeneses nor the factors that define these disease subclasses have been elucidated. The interleukin (IL)-17A autocrine LCH model and IL-17A-targeted therapies have been proposed and have engendered much controversy. Those authors showed high serum IL-17A levels in LCH and argued that serum IL-17A-dependent fusion activities in vitro, rather than serum IL-17A levels, correlated with LCH severity (i.e. the IL-17A paradox). In contrast, others could not confirm the IL-17A autocrine model. So began the controversy on IL-17A, which still continues. We approached the IL-17A controversy and the IL-17A paradox from a new perspective in considering the expression levels of IL-17A receptor (IL-17RA). We detected higher levels of IL-17RA protein expression in LCH-MS (n = 10) as compared to LCH-SS (n = 9) (P = 0.041) by immunofluorescence. We reconfirmed these data by re-analyzing GSE16395 mRNA data. We found that serum levels of IL-17A were higher in LCH (n = 38) as compared to controls (n = 20) (P = 0.005) with no significant difference between LCH subclasses. We propose an IL-17A endocrine model and stress that changes in IL-17RA expression levels are important for defining LCH subclasses. We hypothesize that these IL-17RA data could clarify the IL-17A controversy and the IL-17A paradox. As a potential treatment of LCH-MS, we indicate the possibility of an IL-17RA-targeted therapy.

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  • Morphologic, flow cytometric, functional, and molecular analyses of S100B positive lymphocytes, unique cytotoxic lymphocytes containing S100B protein

    Yukari Miki, Yuka Gion, Yuriko Mukae, Atsushi Hayashi, Hiaki Sato, Tadashi Yoshino, Kiyoshi Takahashi

    EUROPEAN JOURNAL OF HAEMATOLOGY   90 ( 2 )   99 - 110   2013.2

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    Little is known about the S100B+ lymphocytes, which are unique human peripheral blood lymphocytes (PBL) containing the S100B protein. It has recently been shown that S100B is released from various types of S100B+ cells and exhibits varied cytokine-like activities. In this study, we precisely characterized the S100B+ lymphocytes of healthy adults with respect to the proportion in the whole PBL, immunophenotypes, function, and their S100B mRNA expression and also evaluated their S100B-releasing activity upon stimulation. S100B+ lymphocytes were detected in all individuals examined, and the proportion of S100B+ lymphocytes in the whole PBL ranged from 0.42% to 16.15% (mean, 4.21%). In addition, two subtypes of S100B+ lymphocytes, a CTL subtype (CD3+ CD8+ CD16-) and a NK subtype (CD3- CD8- CD16+), were detected. The majority of the CTL subtype of S100B+ lymphocytes expressed the alpha beta-T-cell receptor. Surprisingly, S100B mRNA was detected not only in S100B+ lymphocytes, but also in every S100B- lymphocytes, although the expression levels of S100B mRNA in S100B- lymphocytes were much lower than those of S100B+ lymphocytes. The CTL subtype of S100B+ lymphocytes exhibited blastic morphological changes, proliferated and released S100B upon stimulation with phytohemagglutinin. The NK subtype of S100B+ lymphocytes exhibited morphological NK activity when cocultivated with NK-sensitive target, K-562 cells. Thus, the CTL subtype of S100B+ lymphocytes exhibit the biological characteristics of T cells, while the NK subtype of S100B+ lymphocytes exhibit the characteristics of NK cells. These results suggest that S100B+ lymphocytes are a particular subtype of cytotoxic lymphocytes that play a unique role in antitumor immunity.

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  • Mediastinal gray zone lymphomaに対しRituximab併用DA-EPOCH療法を施行した3症例

    吉岡 尚徳, 佐伯 恭昌, 浅野 豪, 松岡 賢市, 藤井 伸治, 近藤 英生, 前田 嘉信, 品川 克至, 吉野 正, 谷本 光音

    日本内科学会雑誌   102 ( Suppl. )   187 - 187   2013.2

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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   2013.1

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    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.

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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   2013.1

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    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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  • The evaluation of immunohistochemical markers and thymic cortical microenvironmental cells in distinguishing thymic carcinoma from type b3 thymoma or lung squamous cell carcinoma.

    Hayashi A, Fumon T, Miki Y, Sato H, Yoshino T, Takahashi K

    J Clin Exp Hematop   53 ( 1 )   9 - 19   2013

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

    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

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    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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  • Primary intestinal follicular lymphoma: How to identify follicular lymphoma by routine endoscopy.

    Iwamuro M, Kawai Y, Takata K, Kawano S, Yoshino T, Okada H, Yamamoto K

    World J Gastrointest Endosc   5 ( 1 )   34 - 38   2013

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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

    Yasumasa Shimoura, Yasuharu Sato, Katsuyoshi Takata, Yorihisa Orita, Satoko Nakamura, Shyouhei Mano, Tadashi Yoshino

    ACTA CYTOLOGICA   57 ( 1 )   84 - 90   2013

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    Objective: We examined the usefulness of light-chain restriction (LCR) on immunocytochemical double staining (IDS) for cytological diagnosis. Study Design: We investigated LCR on IDS in 40 patients with proliferative lymphatic disorders (23 with B cell lymphoma, 13 with reactive lymphoid lesions, 2 with T cell lymphoma and 2 with Hodgkin's lymphoma). In addition, the results of flow cytometry (FCM) were compared in 34 of these patients. Results: On IDS, LCR was detected in 21 of 23 patients (91.3%) with B cell lymphoma. On FCM, it was detected in 15 of 21 patients (71.4%) with B cell lymphoma. Neither IDS nor FCM showed LCR in any patients with reactive lesions, T cell lymphoma or Hodgkin's lymphoma. Conclusion: IDS facilitated the detection of LCR with a single specimen under morphological observation. The application of this procedure may improve the accuracy of cytological diagnosis. Copyright 2012 S. Karger AG, Basel

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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

    Yasumasa Shimoura, Yasuharu Sato, Katsuyoshi Takata, Yorihisa Orita, Satoko Nakamura, Shyouhei Mano, Tadashi Yoshino

    ACTA CYTOLOGICA   57 ( 1 )   84 - 90   2013

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    Objective: We examined the usefulness of light-chain restriction (LCR) on immunocytochemical double staining (IDS) for cytological diagnosis. Study Design: We investigated LCR on IDS in 40 patients with proliferative lymphatic disorders (23 with B cell lymphoma, 13 with reactive lymphoid lesions, 2 with T cell lymphoma and 2 with Hodgkin's lymphoma). In addition, the results of flow cytometry (FCM) were compared in 34 of these patients. Results: On IDS, LCR was detected in 21 of 23 patients (91.3%) with B cell lymphoma. On FCM, it was detected in 15 of 21 patients (71.4%) with B cell lymphoma. Neither IDS nor FCM showed LCR in any patients with reactive lesions, T cell lymphoma or Hodgkin's lymphoma. Conclusion: IDS facilitated the detection of LCR with a single specimen under morphological observation. The application of this procedure may improve the accuracy of cytological diagnosis. Copyright 2012 S. Karger AG, Basel

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  • Anti-high mobility group box-1 antibody therapy for traumatic brain injury

    Okuma Yu, Liu Keyue, Wake Hidenori, Haruma Jun, Yoshino Tadashi, Ohtsuka Aiji, Takahashi Hideo K, Mori Shuji, Nishibori Masahiro, Date Isao

    Okayama Igakkai Zasshi (Journal of Okayama Medical Association)   125 ( 2 )   97 - 102   2013

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  • EBV-associated T and NK cell lymphoproliferative disorders: Consensus report of the 4th Asian Hematopathology Workshop

    Young-Hyeh Ko, Hyun-Jung Kim, Young-Ha Oh, Geongsin Park, Seung-Sook Lee, Jooryung Huh, Chul-Woo Kim, Insun Kim, Siok-Bian Ng, Soo-Young Tan, Shih-Sung Chuang, Naoya Nakamura, Tadashi Yoshino, Shigeo Nakamura, Hiroshi Kimura, Koichi Ohshima

    Journal of Hematopathology   5 ( 4 )   319 - 324   2012.12

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    T and NK cell proliferative diseases associated with acute and chronic Epstein-Barr virus (EBV) infection are uncommon and raise several clinical issues regarding diagnostic criteria and terminology. This is a summary report of the consensus meeting held in the 4th Asian Hematopathology Workshop. The umbrella term "EBV-positive T/NK lymphoproliferative disease in childhood-type" covers the entire spectrum of EBV-associated lesions in childhood, ranging from reactive to neoplastic processes. Systemic T/NK cell lymphoproliferative disease (LPD) of childhood type is defined as a fulminant disease associated with the proliferation of polyclonal, oligoclonal, or monoclonal T or NK cells and includes aggressive NK cell-associated leukemia in children. Chronic active EBV disease-type T/NK cell LPD is divided into three groups-polymorphic/polyclonal, polymorphic/monoclonal, and monomorphic/monoclonal-based on the histology and clonality of T or NK cells. A monoclonal EBV-positive T/NK cell type of proliferation with the clinical features of chronic active EBV disease rather than the fulminant course of systemic EBV-positive T/NK cell LPD of childhood is considered "chronic active EBV disease-type T/NK cell LPD". Hydroa vacciniforme (HV)-like T cell LPD is defined as a spectrum of EBV-infected T cell proliferative diseases with homing to the skin and is further classified into a classic type, a severe type, and malignant lymphoma. Criteria to define each category of HV-like T cell LPD remain to be clarified. © 2012 Springer-Verlag Berlin Heidelberg.

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  • Extranodal marginal zone lymphoma of the dura: A case report

    Masahiko Yamada, Kazuho Hirahara, Tetsuzou Tomosugi, Takeshi Ishii, Ayumu Taniguchi, Yousuke Nishimuta, Dan Kawahara, Yuko Sadamura, Kouichi Uetsuhara, Kazunori Sueyoshi, Yukie Tashiro, Tadashi Yoshino, Masayoshi Fujii

    Neurological Surgery   40 ( 12 )   1079 - 1085   2012.12

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    The authors present the case of a 65-year-old woman who initially was diagnosed as having intracranial dural B-cell malignant lymphoma. She survived more than 9 years after surgery and radiation. We re-examined the specimens pathologically. Histological findings confirmed an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) that showed numerous IgG4-positive plasma cells. MALT lymphomas are already recognized as a distinct clinico-pathological entity. A primary dural MALT lymphoma is very rare and has a favorable clinical outcome, and patients are expected to have an excellent long-term survival with local therapy alone.

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  • Diagnostic role of 18F-fluorodeoxyglucose positron emission tomography for follicular lymphoma with gastrointestinal involvement

    Masaya Iwamuro, Hiroyuki Okada, Katsuyoshi Takata, Katsuji Shinagawa, Shigeatsu Fujiki, Junji Shiode, Atsushi Imagawa, Masashi Araki, Toshiaki Morito, Mamoru Nishimura, Motowo Mizuno, Tomoki Inaba, Seiyu Suzuki, Yoshinari Kawai, Tadashi Yoshino, Yoshiro Kawahara, Akinobu Takaki, Kazuhide Yamamoto

    WORLD JOURNAL OF GASTROENTEROLOGY   18 ( 44 )   6427 - 6436   2012.11

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    AIM: To investigate the capacity for 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to evaluate patients with gastrointestinal lesions of follicular lymphoma.
    METHODS: This retrospective case series consisted of 41 patients with follicular lymphoma and gastrointestinal involvement who underwent 18F-FDG-PET and endoscopic evaluations at ten different institutions between November 1996 and October 2011. Data for endoscopic, radiological, and biological examinations performed were retrospectively reviewed from clinical records. A semi-quantitative analysis of 18F-FDG uptake was performed for each involved area by calculating the maximum standardized uptake value (SUVmax). Based on the positivity of 18F-FDG uptake in the gastrointestinal lesions analyzed, patients were subdivided into two groups. To identify potential predictive factors for 18F-FDG positivity, these two groups were compared with respect to gender, age at diagnosis of lymphoma, histopathological grade, pattern of follicular dendritic cells, mitotic rate, clinical stage, soluble interleukin-2 receptor levels detected by 18F-FDG-PET, lactate dehydrogenase (LDH) levels, hemoglobin levels, bone marrow involvement, detectability of gastrointestinal lesions by computed tomography (CT) scanning, and follicular lymphoma international prognostic index (FLIPI) risk.
    RESULTS: Involvement of follicular lymphoma in the stomach, duodenum, jejunum, ileum, cecum, colon, and rectum was identified in 1, 34, 6, 3, 2, 3, and 6 patients, respectively. No patient had esophageal involvement. In total, 19/41 (46.3%) patients exhibited true-positive 18F-FDG uptake in the lesions present in their gastrointestinal tract. In contrast, false-negative 18F-FDG uptake was detected in 24 patients (58.5%), while false-positive 18F-FDG uptake was detected in 5 patients (12.2%). In the former case, 2/19 patients had both 18F-FDG-positive lesions and 18F-FDG-negative lesions in the gastrointestinal tract. In patients with 18F-FDG avidity, the SUVmax value of the involved gastrointestinal tract ranged from 2.6 to 17.4 (median: 4.7). For the 18F-FDG-negative (n = 22) and -positive (n = 19) groups, there were no differences in the male to female ratios (10/12 vs 4/15, P = 0.186), patient age (63.6 +/- 2.4 years vs 60.1 +/- 2.6 years, P = 0.323), presence of histopathological grade 1 vs 2 (20/2 and 17/2, P = 1.000), follicular dendritic cell pattern (duodenal/nodal: 13/5 vs 10/3, P = 1.000), mitotic rate (low/ partly high, 14/1 vs 10/3, P = 0.311), clinical stage according to the Ann Arbor system (stages I E and II E/other, 15/7 vs 15/4, P = 0.499), clinical stage according to the Lugano system (stages I and II-1/other, 14/8 vs 14/5, P = 0.489), soluble interleukin-2 receptor levels (495 +/- 78 vs 402 +/- 83, P = 0.884), LDH levels (188 +/- 7 vs 183 +/- 8, P = 0.749), hemoglobin levels (13.5 +/- 0.3 vs 12.8 +/- 0.4, P = 0.197), bone marrow involvement (positive/negative, 1/8 vs 1110, P = 1.000), detectability by CT scanning (positive/negative, 1/16 vs 4/13, P = 0.335), and FLIPI risk (low risk/other, 16/6 vs 13/6, P = 0.763), respectively in each case.
    CONCLUSION: These findings indicate that it is not feasible to predict 18F-FDG-avidity. Therefore, 18F-FDG-PET scans represent a complementary modality for the detection of gastrointestinal involvements in follicular lymphoma patients, and surveillance of the entire gastrointestinal tract by endoscopic examinations is required. (C) 2012 Baishideng. All rights reserved.

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

    Takehiro Tanaka, Atsushi Fujimura, Koichi Ichimura, Hiroyuki Yanai, Yasuharu Sato, Katsuyohi Takata, Hiroyuki Okada, Seiji Kawano, Shunsuke Tanabe, Tadashi Yoshino

    WORLD JOURNAL OF GASTROENTEROLOGY   18 ( 43 )   6263 - 6268   2012.11

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    AIM: To compare the clinicopathological characteristics of human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative Barrett's adenocarcinoma in Japan.
    METHODS: We performed immunohistochemical analysis of HER2 in 30 samples taken from patients with Barrett's adenocarcinoma and dual color in situ hybridization in cases showing 2+ reactions. We compared the clinicopathological characteristics of HER2-positive and HER2-negative patients.
    RESULTS: HER2 positivity was identified in 8 (27%) carcinoma samples. We found that HER2 expression was associated with p53 overexpression (100% vs 52.6% in pT1 tumor; 100% vs 54.5% in all stage tumor, P &lt; 0.05) and protruding lesions at the early disease stage. There was no association between the mucin phenotype of the carcinomas and prognosis. HER2 expression and low clinical stage were unexpectedly different between Barrett's adenocarcinoma patients and gastric cancer patients, but the macroscopic features may be associated with earlier diagnosis in these patients.
    CONCLUSION: Our results suggest that HER2-positive Barrett's adenocarcinomas are associated with p53 overexpression and lesion protrusion at the early disease stage. (C) 2012 Baishideng. All rights reserved.

    DOI: 10.3748/wjg.v18.i43.6263

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  • Serum IL-10 and IL-8 Among Variable Cytokines Derived From Helper T Cells Might Be Associated with Prognoses for Malignant Lymphoma Patients

    Junichi Kitagawa, Hisashi Tsurumi, Naoe Goto, Katsuyoshi Takata, Nobuhiko Nakamura, Nobuhiro Kanemura, Takeshi Hara, Senji Kasahara, Takeshi Takahashi, Tadashi Yoshino, Hisataka Moriwaki

    BLOOD   120 ( 21 )   2012.11

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  • Dual-time-point F-18 FDG PET/CT for evaluation in patients with malignant lymphoma

    Takayoshi Shinya, Soichiro Fujii, Shoji Asakura, Toshitaka Taniguchi, Kotaro Yoshio, Aierken Alafate, Shuhei Sato, Tadashi Yoshino, Susumu Kanazawa

    ANNALS OF NUCLEAR MEDICINE   26 ( 8 )   616 - 621   2012.10

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    The aim of this study was to evaluate the usefulness of F-18 fluorodeoxyglucose (FDG) dual-time-point (DTP) positron emission tomography (PET)/computed tomography (CT) with semiquantitative analyses for the initial staging in patients with malignant lymphoma.
    Forty-three patients had DTP PET/CT, with 60-min and 2-h scan [n = 8, Hodgkin's lymphoma (HL); n = 12, indolent non-Hodgkin lymphoma (NHL); n = 23, aggressive NHL].
    A total of 524 lesions were evaluated (406 lymph nodes and 118 extra-nodal lesions). The maximum standardized uptake value (SUVmax) on 2-h delayed scan (SUV2) was significantly higher than those on 1-h early scan (SUV1) for all groups (P &lt; 0.0001 for HL; P &lt; 0.0001 for indolent NHL; P &lt; 0.0001 for aggressive NHL). Significant differences were detected between HL and indolent NHL, between indolent NHL and the aggressive NHL for both SUV1 and SUV2 (each P &lt; 0.0001). No significant differences were detected between HL and aggressive NHL for both SUV1 and SUV2 (P = 0.6891 for SUV1; P = 0.8828 for SUV2); however, significant differences were detected for the retention index of SUVmax between these groups (P = 0.0238).
    DTP F-18 FDG PET/CT with a semiquantitative technique may have the potential to provide the more accurate diagnoses for the staging of malignant lymphoma and the more important role in predicting the histological grades of malignancy compared with single-time-point F-18 FDG-PET scan.

    DOI: 10.1007/s12149-012-0619-y

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  • Extranodal natural killer/T-cell lymphoma from skin or soft tissue: suggestion of treatment from multinational retrospective analysis

    H. K. Ahn, C. Suh, S. S. Chuang, J. Suzumiya, Y. H. Ko, S. J. Kim, J. R. Huh, D. H. Yoon, S. Y. Oh, J. S. Kim, S. I. Lee, K. W. Park, P. P. Hsieh, S. Nakamura, T. Yoshino, K. Ito, T. Nagatani, K. Oshimi, R. Suzuki, W. S. Kim

    ANNALS OF ONCOLOGY   23 ( 10 )   2703 - 2707   2012.10

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    Clinical features and outcomes of extranodal natural killer/T-cell lymphoma (ENKL) arising from extranasal sites are not fully understood. The purpose of this study was to study the prognosis and treatment outcome of skin/soft tissue primary ENKL.
    This multicenter retrospective study included 48 patients with skin/soft tissue primary ENKL diagnosed from 1993 to 2010.
    Patients with Ann Arbor stage I, T1-2N0M0 by International Society for Cutaneous Lymphomas-European Organization of Research and Treatment of Cancer TNM (tumour-node-metastasis) stage, International prognostic index score of 0-1, and a Korean prognostic index (KPI) score of 0-1 were associated with better survival. Four of five patients with T1-2N0M0 disease achieved complete response with radiation alone. In disseminated disease, only 6 of 13 patients responded to anthracycline-containing chemotherapy, and all the two patients receiving SMILE showed response.
    In conclusion, we identified the prognostic value of KPI, and we suggest a treatment recommendation according to the TNM (tumour-node-metastasis) stage. Radiotherapy with/without chemotherapy seemed to be optimal in localized disease. In advanced stages, a more aggressive treatment regimen with newer agents should be sought.

    DOI: 10.1093/annonc/mds096

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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   2012.10

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    DOI: 10.1002/art.34593

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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   2012.10

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    DOI: 10.1002/art.34593

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  • Mediastinal gray zone lymphomaに対しRituximab併用DA-EPOCH療法を施行した3症例

    佐伯 恭昌, 吉岡 尚徳, 淺野 豪, 黒井 大雅, 長谷川 詠子, 松岡 賢市, 藤井 伸治, 近藤 英生, 前田 嘉信, 品川 克至, 吉野 正, 谷本 光音

    日本癌治療学会誌   47 ( 3 )   2508 - 2508   2012.10

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  • Anti-high mobility group box-1 antibody therapy for traumatic brain injury

    Yu Okuma, Keyue Liu, Hidenori Wake, Jiyong Zhang, Tomoko Maruo, Isao Date, Tadashi Yoshino, Aiji Ohtsuka, Naoki Otani, Satoshi Tomura, Katsuji Shima, Yasuhiko Yamamoto, Hiroshi Yamamoto, Hideo K. Takahashi, Shuji Mori, Masahiro Nishibori

    ANNALS OF NEUROLOGY   72 ( 3 )   373 - 384   2012.9

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    Objective: High mobility group box-1 (HMGB1) plays an important role in triggering inflammatory responses in many types of diseases. In this study, we examined the involvement of HMGB1 in traumatic brain injury (TBI) and evaluated the ability of intravenously administered neutralizing anti-HMGB1 monoclonal antibody (mAb) to attenuate brain injury. Methods: Traumatic brain injury was induced in rats or mice by fluid percussion. Anti-HMGB1 mAb or control mAb was administered intravenously after TBI. Results: Anti-HMGB1 mAb remarkably inhibited fluid percussion-induced brain edema in rats, as detected by T2-weighted magnetic resonance imaging; this was associated with inhibition of HMGB1 translocation, protection of bloodbrain barrier (BBB) integrity, suppression of inflammatory molecule expression, and improvement of motor function. In contrast, intravenous injection of recombinant HMGB1 dose-dependently produced the opposite effects. Experiments using receptor for advanced glycation end product (RAGE)-/-, toll-like receptor-4 (TLR4)-/-, and TLR2-/- mice suggested the involvement of RAGE as the predominant receptor for HMGB1. Interpretation: Anti-HMGB1 mAb may provide a novel and effective therapy for TBI by protecting against BBB disruption and reducing the inflammatory responses induced by HMGB1. ANN NEUROL 2012;72:373384

    DOI: 10.1002/ana.23602

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  • Consensus statement on the pathology of IgG4-related disease

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

    MODERN PATHOLOGY   25 ( 9 )   1181 - 1192   2012.9

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    IgG4-related disease is a newly recognized fibro-inflammatory condition characterized by several features: a tendency to form tumefactive lesions in multiple sites; a characteristic histopathological appearance; and-often but not always-elevated serum IgG4 concentrations. An international symposium on IgG4-related disease was held in Boston, MA, on 4-7 October 2011. The organizing committee comprising 35 IgG4-related disease experts from Japan, Korea, Hong Kong, the United Kingdom, Germany, Italy, Holland, Canada, and the United States, including the clinicians, pathologists, radiologists, and basic scientists. This group represents broad subspecialty expertise in pathology, rheumatology, gastroenterology, allergy, immunology, nephrology, pulmonary medicine, oncology, ophthalmology, and surgery. The histopathology of IgG4-related disease was a specific focus of the international symposium. The primary purpose of this statement is to provide practicing pathologists with a set of guidelines for the diagnosis of IgG4-related disease. The diagnosis of IgG4-related disease rests on the combined presence of the characteristic histopathological appearance and increased numbers of IgG4(+) plasma cells. The critical histopathological features are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. We propose a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy. Tissue IgG4 counts and IgG4:IgG ratios are secondary in importance. The guidelines proposed in this statement do not supplant careful clinicopathological correlation and sound clinical judgment. As the spectrum of this disease continues to expand, we advocate the use of strict criteria for accepting newly proposed entities or sites as components of the IgG4-related disease spectrum. Modern Pathology (2012) 25, 1181-1192; doi:10.1038/modpathol.2012.72; published online 18 May 2012

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  • Histological and immunohistochemical features of gingival enlargement in a patient with AML

    Norihiro Sonoi, Yoshihiko Soga, Hiroshi Maeda, Koichi Ichimura, Tadashi Yoshino, Kazutoshi Aoyama, Nobuharu Fujii, Yoshinobu Maeda, Mitsune Tanimoto, Richard Logan, Judith Raber-Durlacher, Shogo Takashiba

    ODONTOLOGY   100 ( 2 )   254 - 257   2012.7

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    Here, we discuss the pathophysiology of leukemia-associated gingival enlargement based on a case of acute myelomonocytic leukemia (AML-M4) with typical gingival enlargement. Uniquely, this patient was well enough to allow full periodontal examination and incisional gingival biopsy to be performed both before and after chemotherapy. The patient was a 39-year-old Japanese woman with AML-M4 showing gingival enlargement. Histological and immunohistochemical features of gingiva and bacterial counts in the periodontal pockets were examined before and after chemotherapy. The results were as follows: (1) infiltration of myelomonocytic blasts in enlarged gingiva; (2) resolution of gingival enlargement with complete remission of AML by anticancer chemotherapy; and (3) the numbers of bacteria in the periodontal pockets were not high and were not altered before or after chemotherapy. In patients with AML-M4, remarkable mucosal enlargement is not generally observed in the body except in the gingiva. We hypothesized that antigens derived from periodontal bacteria, even if they are not present in large numbers, could act as chemoattractants for myelomonocytic leukemic cells.

    DOI: 10.1007/s10266-011-0051-0

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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   2012.7

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    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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  • Efficacy and Long-Term Follow-up of Helicobacter pylori Eradication Therapy and Radiation Therapy as a Secondary Treatment for Localized Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

    Hiroyuki Okada, Yoshiro Kawahara, Junichiro Nasu, Seiji Kawano, Takao Tsuzuki, Masahide Kita, Minoru Matubara, Keisuke Hori, Sayo Kobayashi, Daisuke Kawai, Takehiro Tanaka, Tadashi Yoshino, Kazuhide Yamamoto

    GASTROENTEROLOGY   142 ( 5 )   S215 - S215   2012.5

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  • 縦隔原発悪性リンパ腫に対しRituximab併用DA-EPOCH療法を施行した2症例

    吉岡 尚徳, 藤原 英晃, 淺野 豪, 廻 勇輔, 黒井 大雅, 長谷川 詠子, 松岡 賢市, 藤井 伸治, 近藤 英生, 前田 嘉信, 品川 克至, 吉野 正, 谷本 光音

    日本リンパ網内系学会会誌   52   124 - 124   2012.5

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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   2012.4

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    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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  • Primary cutaneous CD30 positive T-cell lymphoproliferative disorders with aberrant expression of PAX5: Report of three cases

    Masahiro Hagiwara, Akihiro Tomita, Katsuyoshi Takata, Yoshie Shimoyama, Tadashi Yoshino, Yasushi Tomita, Shigeo Nakamura

    PATHOLOGY INTERNATIONAL   62 ( 4 )   264 - 270   2012.4

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    Accurate diagnosis of lymphoma includes the assessment of lineage-specific markers. Hematopoietic and lymphoid tissues express PAX5 exclusively in pro-B-cell to mature B-cell stages. However, some mature PAX5+ T-cell lymphomas have been reported. We report three cases of primary cutaneous CD30+ T-cell lymphoproliferative disorders (LPDs) with PAX5 expression: one cutaneous anaplastic large cell lymphoma (ALCL) and two cases of lymphomatoid papulosis (LyP). The three patients were 26 years old and female, 75 years old and female, and 65 years old and male. In all cases, Hodgkin's and Reed-Sternberg-like large lymphoid cells were present, positive for CD30, fascin, and PAX5, and negative for CD3, CD4, CD8, CD20, CD45RO, CD56, cytotoxic markers, and Epstein-Barr virus. The ALCL was accompanied by lymphadenopathy; the patient died of progressive disease 5 months after diagnosis. The LyP cases were localized in the skin with spontaneous regression. One case was diagnosed during pregnancy, transformed to ALCL, and ended in death 32 months after diagnosis despite multi-agent chemotherapy. This study is the first to address the clinical significance of PAX5+ primary cutaneous CD30+ T-cell LPDs. These cases were distinct regarding PAX5 expression and a relatively aggressive clinical course versus conventional primary cutaneous CD30+ T-cell LPDs.

    DOI: 10.1111/j.1440-1827.2011.02784.x

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  • Dynamic changes of epigenetic abnormalities during initiation and progression of adult T-cell leukemia/lymphoma (ATLL)

    Takashi Oka, Lamia Abd Al-Kader, Hiaki Sato, Kana Washio, Yoko Shinnou, Katsuyoshi Takata, Ichiro Murakami, Atae Utsunomiya, Tadashi Yoshino

    CANCER RESEARCH   72   2012.4

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    DOI: 10.1158/1538-7445.AM2012-3132

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  • A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details

    Hisanori Umehara, Kazuichi Okazaki, Yasufumi Masaki, Mitsuhiro Kawano, Motohisa Yamamoto, Takako Saeki, Shoko Matsui, Takayuki Sumida, Tsuneyo Mimori, Yoshiya Tanaka, Kazuo Tsubot