Faculty Profiles - SATO Yasuharu

Papers - SATO Yasuharu

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

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

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

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

DOI： 10.1007/s00795-016-0139-2

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

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

AURIS NASUS LARYNX 43 ( 6 ) 648 - 653 2016.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

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

DOI： 10.1016/j.anl.2016.01.009

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

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

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

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

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

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

DOI： 10.1111/cas.13031

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

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

Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

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

DOI： 10.1007/s00262-016-1902-x

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

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

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

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

DOI： 10.3892/mmr.2016.5808

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

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

HEART AND VESSELS 31 ( 10 ) 1709 - 1713 2016.10

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

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

DOI： 10.1007/s00380-016-0794-1

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

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

ARTHRITIS & RHEUMATOLOGY 68 2016.10

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

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

Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

Conclusion: In Kikuchi-Fujimoto disease (KFD), a low ratio of blastic cells (<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 (<70%) in lymph node specimens (p=0.011) and absence of atypical lymphocytes in peripheral blood (p=0.026) were associated with a relatively long duration of KFD.

DOI： 10.3109/00016489.2016.1164895

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

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

HUMAN PATHOLOGY 55 164 - 173 2016.9

Language：English Publishing type：Research paper (scientific journal) Publisher：W B SAUNDERS CO-ELSEVIER INC

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

DOI： 10.1016/j.humpath.2016.05.010

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

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

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

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

DOI： 10.1111/pin.12439

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

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

AMERICAN JOURNAL OF SURGICAL PATHOLOGY 40 ( 4 ) 495 - 501 2016.4

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

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

DOI： 10.1097/PAS.0000000000000575

Glottic cancer in patients without complaints of hoarseness Reviewed

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

HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK 38 E316 - E320 2016.4

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

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

DOI： 10.1002/hed.23992

Castleman's diseaseに類似した組織像を呈するMantle cell lymphomaの2症例

表梨華, 佐藤康晴, 高田尚良, 吉野正

日本病理学会会誌 105 ( 1 ) 557 - 557 2016.4

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

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

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare disease comprising < 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 <= 1, the result of allele-specific polymerase chain reaction for MYD88 corresponded to those of the Sanger sequence at 92.6% sensitivity and 100% specificity. According to Choi's algorithm, 16/27 (59.3%) demonstrated an ABC-like phenotype in PB-DLBCL, and 15/18 (83.3%) demonstrated an ABC-like phenotype in CLB-DLBCL. In conclusion, MYD88 L265P and CD79B mutations were frequently detected in PB-DLBCL, and they may be key molecules associated with PB-DLBCL lymphomagenesis. Further analysis will be required to clarify the mechanism of its pathogenesis.

DOI： 10.1097/PAS.0000000000000592

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

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

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

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

DOI： 10.1002/ajh.24242

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

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

MEDICINE 95 ( 7 ) e2853 2016.2

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

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

DOI： 10.1097/MD.0000000000002853

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

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

IgG4-Related Kidney Disease 187 - 191 2016.1

Language：English Publishing type：Part of collection (book) Publisher：Springer Japan

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

DOI： 10.1007/978-4-431-55687-9_16

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

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

IgG4-Related Kidney Disease 293 - 301 2016.1

Language：English Publishing type：Part of collection (book) Publisher：Springer Japan

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

DOI： 10.1007/978-4-431-55687-9_26

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