研究者業績
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  2. 山田 勢至

山田 勢至

Yamada Seiji

基本情報

所属
藤田医科大学医学部 病理診断学講座 准教授
学位
博士（医学）(名古屋市立大学)
J-GLOBAL ID
201601018477634559
researchmap会員ID
7000016197

研究キーワード

 3

研究分野

 2

経歴

 7
もっとみる

学歴

 2

受賞

 4

論文

 56
  • Eri Ushida, Hidemi Toyoda, Ryo Hanaki, Keishiro Amano, Masahiko Okamoto, Seiji Yamada, Takayuki Nojima, Masahiro Hirayama
    Pediatric blood & cancer 70(12) e30676 2023年12月  
  • Seiji Yamada, Motoki Tanikawa, Yuko Matsushita, Ryota Fujinami, Hiroshi Yamada, Kaishi Sakomi, Tomohiro Sakata, Hidehito Inagaki, Hideaki Yokoo, Koichi Ichimura, Mitsuhito Mase
    Neuropathology : official journal of the Japanese Society of Neuropathology 2023年11月2日  査読有り筆頭著者
    Subependymal giant cell astrocytoma (SEGA) is a low-grade periventricular tumor that is closely associated with tuberous sclerosis complex (TSC). SEGA typically arises during the first two decades of life and rarely arises after the age of 20-25 years. Nevertheless, it has also been reported that glioma histologically resembling SEGA, so-called SEGA-like astrocytoma, can arise in neurofibromatosis type 1 (NF1) patients, even in the elderly. Herein, we report a case of SEGA-like circumscribed astrocytoma arising in the lateral ventricle of a 75-year-old woman. Whole-exome sequencing revealed a somatic variant of NF1. Methylation array analysis led to a diagnosis of "methylation class glioblastoma, IDH-wildtype, mesenchymal-type (GBM, MES)" with a high calibrated score (0.99). EGFR amplification, CDKN2A/B homozygous deletion, chromosomal +7/-10 alterations, and TERT promoter mutation, typical molecular abnormalities usually found in GBM, were also observed. While most reported cases of SEGA-like astrocytoma have arisen in NF1 patients, the patient was neither TSC nor NF1. Near total removal was accomplished with endoscopic cylinder surgery. At the 36-month follow-up, there was no tumor recurrence without adjuvant therapies. This clinical behavior did not match GBM. SEGA-like astrocytoma of the elderly is rare, and this is the oldest case reported so far. In addition, high-grade molecular features found in circumscribed tumor remain unclear. Further investigations among larger series are needed for clarifying the underlying molecular mechanisms.
  • Ayano Michiba, Min Gi, Masanao Yokohira, Eiko Sakurai, Atsushi Teramoto, Yuka Kiriyama, Seiji Yamada, Hideki Wanibuchi, Tetsuya Tsukamoto
    Toxicological sciences : an official journal of the Society of Toxicology 195(2) 202-212 2023年9月28日  
    Direct DNA double-strand breaks result in phosphorylation of H2AX, a variant of the histone H2 protein. Phosphorylated H2AX (γH2AX) may be a potential indicator in the evaluation of genotoxicity and hepatocarcinogenicity. In this study, γH2AX and Ki-67 were detected in the short-term responses (24 h after chemical administration) to classify genotoxic hepatocarcinogens (GHs) from non-GH chemicals. One hundred and thirty-five 6-week-old Crl: CD(SD) (SPF) male rats were treated with 22 chemicals including 11 GH and 11 non-GH, sacrificed 24 h later, and immunostained with γH2AX and Ki-67. Positivity rates of these markers were measured in the 3 liver ZONEs 1-3; portal, lobular, and central venous regions. These values were input into 3 machine learning models-Naïve Bayes, Random Forest, and k-Nearest Neighbor to classify GH and non-GH using a 10-fold cross-validation method. All 11 and 10 out of 11 GH caused significant increase in γH2AX and Ki-67 levels, respectively (P < .05). Of the 3 machine learning models, Random Forest performed the best. GH were identified with 95.0% sensitivity (76/80 GH-treated rats), 90.9% specificity (50/55 non-GH-treated rats), and 90.0% overall correct response rate using γH2AX staining, and 96.2% sensitivity (77/80), 81.8% specificity (45/55), and 90.4% overall correct response rate using Ki-67 labeling. Random Forest model using γH2AX and Ki-67 could independently predict GH in the early stage with high accuracy.
  • Chisako Iriyama, Kenichiro Murate, Sachiko Iba, Akinao Okamoto, Naoe Goto, Hideyuki Yamamoto, Toshiharu Kato, Keichiro Mihara, Takahiko Miyama, Keiko Hattori, Ryoko Kajiya, Masataka Okamoto, Yasuaki Mizutani, Seiji Yamada, Tetsuya Tsukamoto, Yuichi Hirose, Tatsuro Mutoh, Hirohisa Watanabe, Akihiro Tomita
    Cancer medicine 12(16) 16972-16984 2023年8月  
    BACKGROUND: Distinguishing between central nervous system lymphoma (CNSL) and CNS infectious and/or demyelinating diseases, although clinically important, is sometimes difficult even using imaging strategies and conventional cerebrospinal fluid (CSF) analyses. To determine whether detection of genetic mutations enables differentiation between these diseases and the early detection of CNSL, we performed mutational analysis using CSF liquid biopsy technique. METHODS: In this study, we extracted cell-free DNA from the CSF (CSF-cfDNA) of CNSL (N = 10), CNS infectious disease (N = 10), and demyelinating disease (N = 10) patients, and performed quantitative mutational analysis by droplet-digital PCR. Conventional analyses were also performed using peripheral blood and CSF to confirm the characteristics of each disease. RESULTS: Blood hemoglobin and albumin levels were significantly lower in CNSL than CNS infectious and demyelinating diseases, CSF cell counts were significantly higher in infectious diseases than CNSL and demyelinating diseases, and CSF-cfDNA concentrations were significantly higher in infectious diseases than CNSL and demyelinating diseases. Mutation analysis using CSF-cfDNA detected MYD88L265P and CD79Y196 mutations in 60% of CNSLs each, with either mutation detected in 80% of cases. Mutual existence of both mutations was identified in 40% of cases. These mutations were not detected in either infectious or demyelinating diseases, and the sensitivity and specificity of detecting either MYD88/CD79B mutations in CNSL were 80% and 100%, respectively. In the four cases biopsied, the median time from collecting CSF with the detected mutations to definitive diagnosis by conventional methods was 22.5 days (range, 18-93 days). CONCLUSIONS: These results suggest that mutation analysis using CSF-cfDNA might be useful for differentiating CNSL from CNS infectious/demyelinating diseases and for early detection of CNSL, even in cases where brain biopsy is difficult to perform.
  • Makito Tanaka, Hiroki Miura, Soichiro Ishimaru, Gen Furukawa, Yoshiki Kawamura, Kei Kozawa, Seiji Yamada, Fumitaka Ito, Kazuko Kudo, Tetsushi Yoshikawa
    Pediatric reports 15(2) 333-340 2023年5月26日  
    Central nervous system (CNS) involvement in anaplastic large cell lymphoma (ALCL) at diagnosis is rare and leads to poor prognosis with the use of the standard ALCL99 protocol alone. CNS-directed intensive chemotherapy, such as an increased dose of intravenous MTX, increased dose of dexamethasone, intensified intrathecal therapy, and high-dose cytarabine, followed by cranial irradiation, has been shown to improve survival in this population. In this paper, the authors describe a 14-year-old male with an intracranial ALCL mass at onset who received CNS-directed chemotherapy followed by 23.4 Gy of whole-brain irradiation. After the first systemic relapse, the CNS-penetrating ALK inhibitor, alectinib, was applied; it has successfully maintained remission for 18 months without any adverse events. CNS-penetrating ALK inhibitor therapy might prevent CNS relapse in pediatric ALK-positive ALCL. Next-generation ALK inhibitors could be introduced as a promising treatment option, even for primary ALCL with CNS involvement, which could lead to the omission of cranial irradiation and avoid radiation-induced sequalae. Further evidence of CNS-penetrating ALK inhibitor combined therapy for primary ALK-positive ALCL is warranted to reduce radiation-induced sequalae in future treatments.
  • 大場 茂生, 杉原 英志, 山田 勢至, 中江 俊介, 西山 悠也, 武藤 淳, 安達 一英, 安部 雅人, 佐谷 秀行, 廣瀬 雄一
    Brain Tumor Pathology 40(Suppl.) 061-061 2023年5月  
  • Shigeo Ohba, Kazuhiro Murayama, Takao Teranishi, Masanobu Kumon, Shunsuke Nakae, Masao Yui, Kaori Yamamoto, Seiji Yamada, Masato Abe, Mitsuhiro Hasegawa, Yuichi Hirose
    Cancers 15(3) 952-952 2023年2月2日  
    Distinguishing primary central nervous system lymphoma (PCNSL) from glioblastoma, isocitrate dehydrogenase (IDH)-wildtype is sometimes hard. Because the role of operation on them varies, accurate preoperative diagnosis is crucial. In this study, we evaluated whether a specific kind of chemical exchange saturation transfer imaging, i.e., amide proton transfer-weighted (APTw) imaging, was useful to distinguish PCNSL from glioblastoma, IDH-wildtype. A total of 14 PCNSL and 27 glioblastoma, IDH-wildtype cases were evaluated. There was no significant difference in the mean APTw signal values between the two groups. However, the percentile values from the 1st percentile to the 20th percentile APTw signals and the width1–100 APTw signals significantly differed. The highest area under the curve was 0.796, which was obtained from the width1–100 APTw signal values. The sensitivity and specificity values were 64.3% and 88.9%, respectively. APTw imaging was useful to distinguish PCNSL from glioblastoma, IDH-wildtype. To avoid unnecessary aggressive surgical resection, APTw imaging is recommended for cases in which PCNSL is one of the differential diagnoses.
  • Kenichi Nakamura, Susumu Shibasaki, Seiji Yamada, Kazumitsu Suzuki, Akiko Serizawa, Shingo Akimoto, Masaya Nakauchi, Tsuyoshi Tanaka, Kazuki Inaba, Ichiro Uyama, Koichi Suda
    Surgical case reports 8(1) 180-180 2022年9月26日  
    BACKGROUND: A leiomyosarcoma of the gastrointestinal tract is extremely rare. We report a case of jejunal leiomyosarcoma with intestinal intussusception at the angle of Treitz that was successfully treated with laparoscopic resection followed by intracorporeal reconstruction using a delta-shaped anastomosis. CASE PRESENTATION: A 54-year-old man was referred to our hospital due to fatigue and loss of appetite. Blood tests showed anemia. Enteroscopy and subsequent enterography using meglumine sodium amidotrizoate showed easily hemorrhagic tumor (10 cm in diameter) in the jejunum just beyond the angle of Treitz. Contrast-enhanced computed tomography revealed jejunojejunal intussusception. Histopathological examination of a biopsy specimen revealed a leiomyosarcoma. Laparoscopic resection of the tumor without reduction of the intussusception was performed. The resected line of the proximal intestine was very close to the ligament of Treitz in the present case. Intracorporeal jejunojejunostomy was completed using a delta-shaped anastomosis, wherein anastomosis was performed between the posterior walls of the proximal and distal jejunums after minimal mobilization around the ligament of Treitz. The patient's postoperative course was uneventful, and he was discharged at 10 days postoperatively. No recurrence has been observed within 2 years after surgery. CONCLUSIONS: We present a case in which a totally laparoscopic surgery for leiomyosarcoma located at the angle of Treitz with jejunojejunal intussusception was performed successfully.
  • Seiji Yamada, Motoki Tanikawa, Hiromi Shibata, Mai Honda‐Kitahara, Yoshiko Nakano, Kaishi Satomi, Tomohiro Sakata, Takanori Hirose, Koichi Ichimura, Mitsuhito Mase
    Neuropathology 2022年9月7日  査読有り筆頭著者
  • Ayano Michiba, Kazuya Shiogama, Tetsuya Tsukamoto, Masaya Hirayama, Seiji Yamada, Masato Abe
    Acta histochemica et cytochemica 55(4) 111-118 2022年8月27日  
    Macrophages are classified into two phenotypes, M1 and M2, based on their roles. M2 macrophages suppress inflammation and increase in proportion to the malignancy of brain tumors. Recently, macrophage extracellular traps (METs), which change into a network, have been reported as a unique form of macrophage cell death. In this study, immunohistochemical analysis of macrophages in METs in human glioblastoma was performed. To distinguish between M1 and M2 macrophages, multiple immunostainings with Iba1 combined with CD163 or CD204 were performed. M2 macrophages were present in small amounts in normal and borderline areas but showed an increasing trend as they shifted to tumor areas, and most of them were the activated- or phagocytic-type. We also successfully detected METs coexisting with fibrin and lactoferrin near the border between the tumor and necrotic area. M2 macrophages not only suppressed inflammation but also were involved in the formation of METs. This study found that M2 macrophages play various roles in unstable situations.
  • Jun Muto, Yutaka Mine, Yuya Nishiyama, Kazuhiro Murayama, Seiji Yamada, Daijiro Kojima, Motoharu Hayakawa, Kazuhide Adachi, Mitsuhiro Hasegawa, John Y. K. Lee, Yuichi Hirose
    Frontiers in Neuroscience 16 837349-837349 2022年5月4日  
    Meningiomas are a common pathology in the central nervous system requiring complete surgical resection. However, in cases of recurrence and post-irradiation, accurate identification of tumor remnants and a dural tail under bright light remains challenging. We aimed to perform real-time intraoperative visualization of the meningioma and dural tail using a delayed-window indocyanine green (ICG) technique with microscopy. Fifteen patients with intracranial meningioma received 0.5 mg/kg ICG a few hours before observation during the surgery. We used near-infrared (NIR) fluorescence to identify the tumor location. NIR fluorescence could visualize meningiomas in 12 out of 15 cases. Near-infrared visualization during the surgery ranged from 1 to 4 h after the administration of ICG. The mean signal-to-background ratio (SBR) of the intracranial meningioma in delayed-window ICG (DWIG) was 3.3 ± 2.6. The ratio of gadolinium-enhanced T1 tumor signal to the brain (T1BR) (2.5 ± 0.9) was significantly correlated with the tumor SBR (p = 0.016). Ktrans, indicating blood–brain barrier permeability, was significantly correlated with tumor SBR (p &amp;lt; 0.0001) and T1BR (p = 0.013) on dynamic contrast-enhanced magnetic resonance imaging (MRI). DWIG demonstrated a sensitivity of 94%, specificity of 38%, positive predictive value (PPV) of 76%, and negative predictive value (NPV) of 75% for meningiomas. This is the first pilot study in which DWIG fluorescence-guided surgery was used to visualize meningioma and dural tail intraoperatively with microscopy. DWIG is comparable with second-window ICG in terms of mean SBR. Gadolinium-enhanced T1 tumor signal may predict NIR fluorescence of the intracranial meningioma. Blood–brain barrier permeability as shown by Ktrans on dynamic contrast-enhanced MRI can contribute to gadolinium enhancement on MRI and to ICG retention and tumor fluorescence by NIR.
  • Tomoya Horiguchi, Tetsuya Tsukamoto, Yoko Toyama, Toshiharu Sasaki, Tomoyuki Nakamura, Aki Sakurai, Naohide Kuriyama, Satoshi Komatsu, Yoshiko Shigeyasu, Takuma Ina, Eiko Sakurai, Noriko Nakajima, Arisa Tsuchimori, Seiji Yamada, Tadaki Suzuki, Kazuyoshi Imaizumi
    Respirology case reports 10(3) e0912 2022年3月  
    Secondary fungal infections are a critical problem that accompany immunosuppressive therapy for severe coronavirus disease 2019 (COVID-19). We report a fatal case of COVID-19 with disseminated mucormycosis diagnosed during autopsy. A 58-year-old man with diabetes was hospitalized for severe COVID-19 and treated with remdesivir, systemic steroids and tocilizumab. Following treatment, he was provided extracorporeal membrane oxygenation support. However, he died of multiple organ failure accompanied by pulmonary and kidney infarction, as revealed by computed tomography. Autopsy revealed that the infarction was caused by thromboangiitis due to mucormycosis in the brain, lungs, heart, liver and kidneys. Therefore, the diagnosis of disseminated mucormycosis was established. Disseminated mucormycosis is a rare complication of COVID-19. Although its early diagnosis is difficult, the disease progresses rapidly. Hence, we propose that immunosuppressive treatment for COVID-19 should be administered with caution considering the risk of developing severe opportunistic infections, such as mucormycosis.
  • Kazunori Nakaoka, Senju Hashimoto, Naoto Kawabe, Teiji Kuzuya, Seiji Yamada, Akira Sawaki, Kohei Funasaka, Mitsuo Nagasaka, Yoshihito Nakagawa, Ryoji Miyahara, Tomoyuki Shibata, Tetsuya Tsukamoto, Yoshiki Hirooka
    Clinical journal of gastroenterology 15(1) 256-262 2022年2月  
    Pancreatic neuroendocrine neoplasms (PNENs) are relatively rare with a reported incidence of 1-2/100,000 and generally thought to originate from the precursor of the neuroendocrine cells including the islet and the pancreatic duct cells. About 65% of PNENs are non-functional. While insulinomas and gastrinomas are the most common functional PNENs, ACTH-producing PNENs are extremely rare. We herein present an extremely rare case of a patient with Cushing's syndrome caused by PNEN. A 46-year-old woman with edema in bilateral lower extremities and moon face was admitted with a suspicious pancreatic tumor. Enhanced computed tomography and endoscopic ultrasonography revealed a pancreatic tumor. The final diagnosis of ACTH-producing PNEN with Cushing's syndrome was based on clinical and biochemical test results and endocrinological studies. The symptoms associated Cushing's syndrome improved after pancreaticoduodenectomy for PNEN.
  • 武藤淳, 西山悠也, 山田勢至, 牧野真樹, 鈴木敦詞, 長谷川光広, 廣瀬雄一
    日本内分泌学会雑誌 97(S.HPT) 10-12 2021年9月20日  
  • Seiji Yamada, Jun Muto, Sachiko Iba, Kazuya Shiogama, Yuta Tsuyuki, Akira Satou, Shigeo Ohba, Kazuhiro Murayama, Yasuo Sugita, Shigeo Nakamura, Hideaki Yokoo, Akihiro Tomita, Yuichi Hirose, Tetsuya Tsukamoto, Masato Abe
    Neuropathology : official journal of the Japanese Society of Neuropathology 41(5) 335-348 2021年7月13日  査読有り筆頭著者責任著者
    Primary central nervous system lymphomas (PCNSLs) rarely exhibit intratumoral hemorrhage. The differential diagnosis of hemorrhagic neoplasms of the central nervous system (CNS) currently includes metastatic carcinomas, melanomas, choriocarcinomas, oligodendrogliomas, and glioblastomas. Here we present the clinical, radiological, pathological, and molecular genetic features of six cases of PCNSL associated with intratumoral hemorrhage. The median age of patients was 75 years, with male predominance. While conventional PCNSLs were associated with low cerebral blood volume (CBV), perfusion magnetic resonance imaging (MRI) revealed elevated CBV in three cases, consistent with vascular proliferation. All six cases were diagnosed pathologically as having diffuse large B-cell lymphoma (DLBCL) with a non-germinal center B-cell-like (non-GCB) phenotype; marked histiocytic infiltrates and abundant non-neoplastic T-cells were observed in most cases. Expression of vascular endothelial growth factor and CD105 in the lymphoma cells and the small vessels, respectively, suggested angiogenesis within the neoplasms. Neoplastic cells were immunohistochemically negative for programmed cell death ligand 1 (PD-L1), while immune cells in the microenvironment were positive for PD-L1. Mutations in the MYD88 gene (MYD88) (L265P) and the CD79B gene (CD79B) were detected in five and one case, respectively. As therapeutic modalities used for PCNSLs differ from those that target conventional hemorrhagic neoplasms, full tissue diagnoses of all hemorrhagic CNS tumors are clearly warranted.
  • 田中 真己人, 三浦 浩樹, 小澤 慶, 石丸 聡一郎, 河村 吉紀, 吉川 哲史, 工藤 寿子, 渡邉 俊介, 安井 稔博, 村山 未佳, 土屋 智寛, 近藤 靖浩, 宇賀 菜緒子, 直江 篤樹, 原 普二夫, 鈴木 達也, 山田 勢至, 浦野 誠
    日本小児血液・がん学会雑誌 58(1) 65-66 2021年6月  
  • Masanobu Kumon, Shunsuke Nakae, Kazuhiro Murayama, Takema Kato, Shigeo Ohba, Joji Inamasu, Seiji Yamada, Masato Abe, Hikaru Sasaki, Yoshiharu Ohno, Mitsuhiro Hasegawa, Hiroki Kurahashi, Yuichi Hirose
    Neurologia medico-chirurgica 61(8) 453-460 2021年6月1日  
    Isocitrate dehydrogenase (IDH) wild-type diffuse astrocytic tumors tend to be pathologically diagnosed as glioblastomas (GBMs). We previously reported that myoinositol to total choline (Ins/Cho) ratio in GBMs on magnetic resonance (MR) spectroscopy was significantly lower than that in IDH-mutant gliomas. We then hypothesized that a low Ins/Cho ratio is a poor prognosis factor in patients with GBMs, IDH-wild-type. In the present study, we calculated the Ins/Cho ratios of patients with GBMs and investigated their progression-free survival (PFS) and overall survival (OS) to determine their utility as prognostic marker. We classified patients with GBMs harboring wild-type IDH (n = 27) into two groups based on the Ins/Cho ratio, and compared patient backgrounds, pathological findings, PFS, OS, and copy number aberrations between the high and low Ins/Cho groups. Patients with GBMs in the low Ins/Cho ratio group indicated shorter PFS (P = 0.021) and OS (P = 0.048) than those in the high Ins/Cho group. Multivariate analysis demonstrated that the Ins/Cho ratio was significantly correlated with PFS (hazard ratio 0.24, P = 0.028). In conclusion, the preoperative Ins/Cho ratio can be used as a novel potential prognostic factor for GBM, IDH-wild-type.
  • Shunsuke Nakae, Masanobu Kumon, Kazuhiro Murayama, Shigeo Ohba, Hikaru Sasaki, Joji Inamasu, Kiyonori Kuwahara, Seiji Yamada, Masato Abe, Yuichi Hirose
    Scientific reports 11(1) 7927-7927 2021年4月12日  
    Seizures are common in patients with gliomas; however, the mechanisms of epileptogenesis in gliomas have not been fully understood. This study hypothesized that analyzing quantified metabolites using magnetic resonance spectroscopy (MRS) might provide novel insights to better understand the epileptogenesis in gliomas, and specific metabolites might be indicators of preoperative seizures in gliomas. We retrospectively investigated patient information (gender, age at diagnosis of tumor, their survival time) and tumor information (location, histology, genetic features, and metabolites according to MRS) in patients with gliomas. The data were correlated with the incidence of seizure and analyzed statistically. Of 146 adult supratentorial gliomas, isocitrate dehydrogenase (IDH) mutant tumors significantly indicated higher incidence of preoperative seizures than IDH wild-type gliomas. However, MRS study indicated that glutamate concentration in IDH wild-type gliomas was higher than that in IDH mutant gliomas. Glutamate was not associated with high frequency of preoperative seizures in patients with gliomas. Instead, increased total N-acetyl-L-aspartate (tNAA) was significantly associated with them. Moreover, multivariable analysis indicated that increased level of tNAA was an independent predictor of preoperative seizures. According to MRS analysis, tNAA, rather than glutamate, might be a useful to detect preoperative seizures in patient with supratentorial gliomas.
  • 福島 英彦, 岩田 洋平, 榊原 潤, 山北 高志, 山田 勢至, 塚本 徹哉, 杉浦 一充
    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集 36回 104-104 2020年12月  
  • Kiyonori Kuwahara, Shigeo Ohba, Kazuyasu Matsumura, Saeko Higashiguchi, Daijiro Kojima, Jun Muto, Shunsuke Nakae, Yuya Nishiyama, Seiji Yamada, Kazuhide Adachi, Masato Abe, Mitsuhiro Hasegawa, Yuichi Hirose
    Neuro-Oncology Advances 2(Supplement_3) ii18-ii18 2020年11月1日  
    Abstract Background: Although high dose-methotrexate therapy has been performed for primary central nervous system malignant lymphoma (PCNSL), R-MPV (rituximab, methotrexate (MTX), procarbazine and vincristine) therapy is currently the first line therapy for (PCNSL) in our hospital. This study examines the results of R-MPV therapy comparing with past treatment. Method/Subjects: Thirty-seven patients treated at our hospital from 2009 to 2020 were included. Overall survival time, progression free survival time, and toxicities were evaluated. Results: The average age of patients was 65.7 years. Patients included 21 males and 16 females. Thirty-six patients were diagnosed DLBCL by resected brain tumor tissues, and one was diagnosed DLBCL by vitreous biopsy. As initial treatment, rituximab±HD-MTX therapy (R±MTX group) was performed in 20 cases, HD-MTX therapy plus radiation (R±MTX+RT group) was performed in 12 cases, and RMPV therapy was performed in 5 cases (R-MPV group). Median OS of all cases was 69 months and median PFS was 38 months. Median OS was 69 months in R±MTX group and could not be calculated in R±MTX+RT, and R-MPV groups. Median PFS was 16 months and 56 months in R±MTX group and R±MTX+RT, respectively, and could not be calculated in the R-MPV group. Although the R-MPV group had a short follow-up period, the results were considered to be comparable to those of the R±MTX+RT group. On the other hand, grade 3/4 adverse events occurred in 50%, 25%, and 100%, respectively. Conclusion: R-MPV therapy may delay the timing of radiation and reduce the amount of radiation. On the other hand, the frequency of adverse events is high, and more strict management of treatment is required.
  • 桑原 聖典, 中原 一郎, 松本 省二, 須山 嘉雄, 盛岡 潤, 長谷部 朗子, 田邊 淳, 陶山 謙一郎, 山田 勢至, 早川 基治, 安倍 雅人, 廣瀬 雄一
    脳血管内治療 5(Suppl.) 14-14 2020年11月  
  • 宮坂 勇平, 吉本 由哉, 村田 和俊, 野田 真永, 安藤 謙, 江原 威, 小此木 範之, 神沼 拓也, 山田 勢至, 伊古田 勇人, 横尾 英明, 大野 達也, 中野 隆史
    日本放射線影響学会大会講演要旨集 63回 64-64 2020年10月  
  • 宮坂 勇平, 吉本 由哉, 村田 和俊, 野田 真永, 安藤 謙, 江原 威, 小此木 範之, 神沼 拓也, 山田 勢至, 伊古田 勇人, 横尾 英明, 大野 達也, 中野 隆史
    日本放射線影響学会大会講演要旨集 63回 122-122 2020年10月  
  • 山田 勢至, 武藤 淳, 村山 和宏, 熊井 惟志, 伊藤 圭介, 井上 辰志, 信澤 純人, 廣瀬 雄一, 安倍 雅人
    Brain Tumor Pathology 37(Suppl.) 139-139 2020年8月  
  • Shigeo Ohba, Kazuhiro Murayama, Kiyonori Kuwahara, Eriel Sandika Pareira, Shunsuke Nakae, Yuya Nishiyama, Kazuhide Adachi, Seiji Yamada, Hikaru Sasaki, Naoki Yamamoto, Masato Abe, Joydeep Mukherjee, Mitsuhiro Hasegawa, Russell O Pieper, Yuichi Hirose
    Neurosurgery 87(2) 408-417 2020年8月1日  査読有り
    BACKGROUND: The extent of resection has been reported to be associated with overall survival in gliomas. The use of 5-aminolevulinic acid (5-ALA) has been recognized to increase the extent of tumor resection. OBJECTIVE: To evaluate what factors affect the intraoperative fluorescence after administration of 5-ALA in gliomas. METHODS: Correlation of intraoperative fluorescence and several clinical, radiographic, molecular biologic, and histopathologic characters was retrospectively evaluated in 104 patients (53 males and 51 females; mean age 54.2 yr) with gliomas at our institution. To clarify the mechanisms that mutant isocitrate dehydrogenase (IDH) affect the intraoperative fluorescence, in Vitro experiments using genetically engineered glioma cells harboring mutant IDH1 were performed. RESULTS: Intraoperative fluorescence was observed in 82 patients (78.8%). In addition to age, magnetic resonance imaging enhancement, World Health Organization grades, and MIB-1 index, the status of IDH was revealed to be correlated with intraoperative fluorescence. In Vitro assay revealed that mutant IDH indirectly reduced the amount of exogenous 5-ALA-derived protoporphyrinogen IX in glioma cells by increasing activity of ferrochelatase and heme oxygenase 1. CONCLUSION: Mutant IDH1/2-induced metabolite changes of exogenous 5-ALA were suggested to contribute to the lesser intraoperative fluorescence in gliomas with mutant IDH1/2 than in those without.
  • Takao Teranishi, Shigeo Ohba, Yushi Kawazoe, Kazuhide Adachi, Kazuhiro Murayama, Seiji Yamada, Masato Abe, Mitsuhiro Hasegawa, Yuichi Hirose
    Neurology India 68(4) 894-894 2020年7月  
    Superficial siderosis is a rare disease resulting from the deposited hemosiderin owing to repeated subarachnoid hemorrhage. It has been reported that hemosiderin deposits on the brain surface and brain parenchyma causes nerve disorder, resulting in progressive and irreversible hearing loss, cerebellar ataxia and pyramidal disorder. The brain tumor is one of the cause of superficial siderosis. A 16-year-old female present a nearby hospital with complaints of absence seizure. A magnetic resonance imaging (MRI) revealed a heterogeneously enhanced mass at the right temporal lobe. Susceptibility-weighted imaging revealed diffuse and extensive superficial siderosis on the brain surface. The tumor was gross totally removed and diagnosed as glioneuronal tumor. The patient had been well, although susceptibility-weighted imaging performed one year after the surgery showed superficial siderosis remained. Early diagnosis and prevention of bleeding sources are recommended to prevent symptom progression associated with superficial siderosis. Susceptibility-weighted imaging is considered useful for early detection of superficial siderosis.
  • Seiji Yamada, Jun Muto, John Clemente Aniceto De Leon, Tadashi Kumai, Keisuke Ito, Kazuhiro Murayama, Natsuko Hama, Yoshiko Nakano, Kaishi Satomi, Yasuhito Arai, Tatsuhiro Shibata, Tatsushi Inoue, Sumihito Nobusawa, Koichi Ichimura, Yuichi Hirose, Masato Abe
    Brain tumor pathology 37(3) 111-117 2020年7月  査読有り筆頭著者責任著者
    The CIC-DUX4 translocation is the most common genetic alteration of small round cell sarcomas without EWSR1 rearrangement. These "Ewing-like sarcomas" usually occur in peripheral soft tissues, and rare primary central nervous system (CNS) tumors have been described. We report a rare case of primary spinal intramedullary Ewing-like sarcoma harboring CIC-DUX4 translocation. A 23-year-old man presented with weakness in the extremities. Magnetic resonance imaging revealed a large intramedullary tumor spanning C3-C5 with heterogeneous enhancement following gadolinium administration. Histologically, most of the tumor displayed dense myeloid proliferation composed of medium- to slightly small-sized primitive cells. Postoperatively, he received local adjuvant radiation therapy without tumor progression for 10 months. Target RNA sequencing analysis revealed the CIC-DUX4 fusion gene. Methylation array analysis resulted in a diagnosis of "methylation class CNS Ewing sarcoma family tumor with CIC alteration". Although this tumor lacked characteristic histological features such as lobular structures in association with desmoplastic stroma, relatively uniform nuclei with prominent nucleoli and eosinophilic cytoplasm, which are often found in CIC-rearranged sarcomas of soft tissue, were identified. Recently, many CNS and soft tissue tumors require genetic analysis for precise diagnosis. To consider certain molecular testing, careful histological examination is essential.
  • 山田 勢至, 浦野 誠, 塚本 徹哉, 黒田 誠
    日本小児血液・がん学会雑誌 57(1) 51-51 2020年6月  
  • Shigeo Ohba, Kiyonori Kuwahara, Seiji Yamada, Masato Abe, Yuichi Hirose
    Brain tumor pathology 37(2) 33-40 2020年4月  査読有り
    According to the 2016 World Health Organization (WHO) classification of central nervous system tumors, diffuse astrocytic and oligodendroglial tumors are differentiated by the presence of isocitrate dehydrogenase 1 or 2 (IDH1/2) mutation and the combined loss of the short arm of chromosome 1 and the long arm of chromosome 19 (1p/19q co-deletion). IDH-mutant astrocytoma often has p53 and alpha-thalassemia/mental retardation syndrome X-linked (ATRX) mutation, showing the alternative lengthening of telomeres (ALT) phenotype, while IDH-mutant and 1p/19q-co-deleted oligodendroglioma often have wild-type p53 and telomerase reverse transcriptase (TERT) promoter mutation, showing telomerase activation. This study analyzed IDH, ATRX, and TERT promoter mutations, and the correlation between them. Immortalized cells overcome the telomere-related crisis by activating telomerase or ALT. In glioma, telomerase is mainly activated by TERT promoter mutation, while ALT is usually associated with ATRX mutation. Although the mechanism of how ATRX mutation induces ALT remains unclear, ATRX loss alone is believed to be insufficient to induce ALT. Treatments targeting telomere maintenance are promising.
  • Yuhei Miyasaka, Yuya Yoshimoto, Kazutoshi Murata, Shin-Ei Noda, Ken Ando, Takeshi Ebara, Noriyuki Okonogi, Takuya Kaminuma, Seiji Yamada, Hayato Ikota, Hideaki Yokoo, Tatsuya Ohno, Takashi Nakano
    Journal of radiation research 61(2) 275-284 2020年3月23日  査読有り
    The current study aimed to evaluate the outcomes of patients with adenocarcinoma (AC) of the uterine cervix after definitive radiotherapy (RT) and to evaluate prognostic factors, including immunity-related molecules. A total of 71 patients with AC of the uterine cervix from multiple Japanese institutions were retrospectively analysed. Histological subtypes were diagnosed according to the 2014 World Health Organization classification. All patients underwent definitive RT comprising external beam RT and intracavitary brachytherapy with or without concurrent chemotherapy. Immunohistochemical studies were performed to detect the expression of programmed cell death-ligand 1(PD-L1) and CD8. The 5-year locoregional control (LC), overall survival (OS) and progression-free survival (PFS) rates for all patients were 61.8, 49.7 and 36.1%, respectively. The LC, OS and PFS rates were not significantly different among the histological subtypes. Membranous PD-L1 expression was not significantly associated with prognosis. Patients with CD8-positive tumor-infiltrating lymphocytes (CD8+TILs) in the tumor nests had significantly better OS than patients without CD8+TILs in the tumor nests (5-year OS: 53.8 vs 23.8%, P = 0.038). As expected, the International Federation of Gynecology and Obstetrics (FIGO) stage (2008) III-IVA and maximum tumor diameter > 40 mm were significantly associated with worse prognosis. In summary, the presence of CD8+TILs in the tumor nests has the potential to be an independent favorable prognostic factor for patients with AC of the uterine cervix after definitive RT.
  • 道場 彩乃, 塩竈 和也, 平山 将也, 山田 勢至, 尾之内 高慶, 金子 千之, 柳田 隆正, 塚本 徹哉, 安倍 雅人
    日本病理学会会誌 109(1) 498-498 2020年3月  
  • 島 寛太, 櫻井 浩平, 酒井 康弘, 山田 勢至, 中川 満, 岡部 麻子, 黒田 誠, 塚本 徹哉, 松山 篤二, 浦野 誠
    日本病理学会会誌 109(1) 346-346 2020年3月  
  • 浦野 誠, 川島 佳晃, 藤原 真紀, 伊藤 里美, 竹内 沙弥花, 須藤 健助, 磯村 まどか, 桑原 一彦, 中川 満, 岡部 麻子, 酒井 康弘, 山田 勢至
    日本臨床細胞学会雑誌 59(1) 30-37 2020年1月  査読有り
    目的：当施設における唾液腺細胞診ミラノシステムの運用と有用性の検討を行った。方法:唾液腺および頸部腫瘤に対する穿刺細胞診施行106例中、組織診断が得られた70例についてミラノシステムを用いて検討し、各診断カテゴリーにおけるrisk of malignancy(ROM)を算出し、細胞診断と組織診断の不一致例について検討した。 成績：70例の内訳は「不適正」16例(以下ROM0%)、「非腫瘍性」3例(33%)、「意義不明な異型」9例(56%)、「良性腫瘍」20例(0%)、「良悪性不明な腫瘍」8例(63%)、「悪性の疑い」4例(100%)、「悪性」10例(100%)であった。富リンパ球性病変、低悪性の癌腫は判定が困難であった。対象を頸部リンパ節を除く唾液腺病変に限るとAUS、SUMPカテゴリーのROMは低下した。 結論：ミラノシステムは不適正の判断を明確化し、従来の鑑別困難をAUS、SUMPとして、臨床医にROMに基づく適切な取り扱い指針を示すことが可能である。ミラノシステムは唾液腺病変を対象としているが、実臨床ではリンパ節を区別して穿刺することは容易でなく、臨床像との対比や補助診断を用いてROMを下げる努力をすべきである。
  • 福島 英彦, 岩田 洋平, 齋藤 健太, 渡邊 総一郎, 杉浦 一充, 山田 勢至, 塚本 徹哉
    日本皮膚科学会雑誌 130(1) 102-102 2020年1月  
  • 花松 智武, 村山 和宏, 西山 悠也, 小濱 佑樹, 植田 高弘, 池田 裕隆, 山田 勢至, 安倍 雅人, 大野 良治, 外山 宏
    映像情報Medical 52(1) 84-85 2020年1月  
  • Kiyonori Kuwahara, Shigeo Ohba, Shunsuke Nakae, Natsuki Hattori, Eriel Sandika Pareira, Seiji Yamada, Hikaru Sasaki, Masato Abe, Mitsuhiro Hasegawa, Yuichi Hirose
    Brain tumor pathology 36(4) 135-143 2019年10月  査読有り
    The genetic features of isocitrate dehydrogenase-wild-type (IDH-wt) lower-grade gliomas (LGGs; World Health Organization grades II and III) are not well defined. This study analyzed the genetic and other features of IDH-wt LGGs to develop a subclassification that can be used to predict their prognosis. Clinical, histopathological, and genetic features of 35 cases of diffuse IDH-wt astrocytoma and IDH-wt anaplastic astrocytoma were analyzed. The following genetic factors were examined: mutations of B-rapidly accelerated fibrosarcoma, telomerase reverse transcriptase promoter (TERTp), histone 3 family 3A, and alpha-thalassemia/mental retardation syndrome, X-linked; and copy number aberrations. In the univariate analysis, the following factors were associated with poor overall survival (OS): the histopathological diagnosis, TERTp mutation, the gain of chromosome 7 (+ 7), and the loss of chromosome 10q (- 10q). In the multivariate analysis, + 7, - 10q, and TERTp mutation were independent prognostic factors associated with poor OS. The median OS was significantly worse for patients who harbored at least one of these factors than for those without any of them (18.5 vs. 54.5 months, P = 0.002). The subclassification of IDH-wt LGGs according to the genetic factors + 7, - 10q, and TERTp mutation is potentially useful for predicting the prognosis.
  • Shigeo Ohba, Kazuhiro Murayama, Yuya Nishiyama, Kazuhide Adachi, Seiji Yamada, Masato Abe, Mitsuhiro Hasegawa, Yuichi Hirose
    World neurosurgery 130 e383-e392 2019年10月  査読有り
    OBJECTIVE: Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) and meningioma exhibit similar radiographic features; however, they differ in their prognoses. Preoperative differentiation between them is important for determining the treatment and follow-up plan. The aim of this study was to determine the factors that can be used to differentiate SFT/HPC from meningioma and World Health Organization (WHO) grade I from grade II meningioma. METHODS: The analysis included 84 cases: 5 of SFT/HPC, 72 of WHO grade I meningioma, and 7 of WHO grade II meningioma. Clinical characteristics and conventional magnetic resonance imaging, perfusion magnetic resonance imaging, and magnetic resonance spectroscopy (MRS) LCModel parameters were evaluated via multivariate logistic regression analysis to identify the factors that distinguish SFT/HPC from meningioma. RESULTS: Patients with SFT/HPC were mostly men and were younger than those with meningioma. The percentage of T2-weighted images in meningioma was greater than that in SFT/HPC. There were significant differences between SFT/HPC and meningioma in levels of glutamate, phosphocholine, myo-inositol, or glycerophosphocholine + phosphocholine derived from long echo-time MRS, and myo-inositol derived from short echo-time MRS. Stepwise logistic regression analysis revealed that the age of <45 years and myo-inositol in short echo-time MRS of ≧6.347 were associated with a diagnosis of SFT/HPC with high sensitivity and specificity. However, no factors were found that differentiated WHO grade I meningioma from WHO grade II meningioma. CONCLUSIONS: Age and myo-inositol level calculated from MRS are useful factors for distinguishing SFT/HPC from meningioma preoperatively.
  • Shigeo Ohba, Yasuhiro Yamada, Kazuhiro Murayama, Eriel Sandika, Hikaru Sasaki, Seiji Yamada, Masato Abe, Mitsuhiro Hasegawa, Yuichi Hirose
    World neurosurgery 126 e1042-e1049 2019年6月  査読有り
    OBJECTIVE: c-Met has been shown to be associated with tumor growth in several human cancers. This study aims to evaluate the correlation between the c-Met expression and histopathologic/clinical characteristics. METHODS: A total of 153 patients with histologically defined World Health Organization grade II-IV diffuse astrocytic and oligodendroglial tumors were analyzed. RESULTS: For each histopathologic diagnosis, the number of cases and positive rate of c-Met expression are as follows: oligodendroglioma, IDH-mutant, and 1p19q codeletion (OD): 16 cases, 6.3%; anaplastic oligodendroglioma, IDH-mutant, and 1p19q codeletion (AO): 11 cases, 36.4%; diffuse astrocytoma (DA), IDH-mutant: 21 cases, 28.6%; anaplastic astrocytoma (AA), IDH- mutant: 15 cases, 20%; glioblastoma, IDH-mutant: 2, 100%, DA, IDH-wildtype: 9 cases, 33.3%; AA, IDH-wildtype: 20 cases, 30.0%; and glioblastoma, IDH-wildtype: 59 cases, 52.5%. c-Met expression was correlated with progression-free survival in oligodendroglial tumors and glioblastoma, IDH-wildtype. Furthermore, it was correlated with overall survival in AO, oligodendroglial tumors, DA, IDH-mutant, DA, IDH-wildtype, and glioblastoma, IDH-wildtype, and tend to be correlated with overall survival in IDH-mutant lower-grade astrocytic tumors. CONCLUSIONS: c-Met expression was revealed to be a useful marker for prognosis prediction in IDH-mutant lower-grade gliomas and glioblastoma, IDH-wildtype, representing a new independent prognostic marker that can be easily measured.
  • Seiji Yamada, Sumihito Nobusawa, Tatsuya Yamazaki, Takao Teranishi, Sadayoshi Watanabe, Kazuhiro Murayama, Shigeo Ohba, Asako Okabe, Kouhei Sakurai, Makoto Urano, Tetsuya Tsukamoto, Hideaki Yokoo, Yuichi Hirose, Masato Abe
    Pathology international 69(6) 372-377 2019年6月  査読有り筆頭著者責任著者
    Glioneuronal tumor (GNT) is a rare central nervous system neoplasm composed of glial and neuronal components. Making the specific diagnosis of GNT can be challenging due to histopathological and genetical similarities among some GNTs and low-grade gliomas. We report a case of GNT with rosette-forming glioneuronal tumor, dysembryoplastic neuroepithelial tumor, and pilocytic astrocytoma-like morphology harboring FGFR1 mutation. A 16-year-old female presented with absence seizures. Magnetic resonance imaging revealed a right temporal lobe mass with multinodular enhancement by gadolinium administration. The tumor was mostly composed of oligodendrocyte-like cells (OLCs) with variable perinuclear haloes. Abundant Rosenthal fibers and eosinophilic granular bodies were identified. Neither mitotic figures nor areas of necrosis were seen. Focal neurocytic rosette features, involving ring-like arrays of OLCs around eosinophilic cores, were observed. Direct sequencing showed a missense mutation in FGFR1 K656E, whereas FGFR1 N546K, PIK3CA, and BRAF V600E were intact. KIAA1549-BRAF fusion was not detected by fluorescence in situ hybridization analysis.
  • 山城 慧, 山田 勢至, 大見 達夫, 安倍 雅人, 長谷川 光広, 廣瀬 雄一
    Brain Tumor Pathology 36(Suppl.) 076-076 2019年5月  
  • 大場 茂生, 村山 和宏, 中江 俊介, 安達 一英, 西山 悠也, 佐々木 光, 山田 勢至, 安倍 雅人, 長谷川 光広, 廣瀬 雄一
    Brain Tumor Pathology 36(Suppl.) 084-084 2019年5月  
  • 渡邉 俊介, 原 普二夫, 土屋 智寛, 近藤 靖浩, 直江 篤樹, 宇賀 菜緒子, 安井 稔博, 鈴木 達也, 三浦 浩樹, 田中 真己人, 工藤 寿子, 吉川 哲史, 山田 勢至, 浦野 誠
    日本小児血液・がん学会雑誌 56(1) 70-71 2019年4月  
  • 山田 勢至, 西尾 知子, 若子 哲, 吉本 純平, 粥川 哲, 酒井 康弘, 浦野 誠, 塚本 徹哉, 黒田 誠, 安倍 雅人
    日本病理学会会誌 108(1) 424-424 2019年4月  
  • Sayumi Tahara, Tomomitsu Tahara, Noriyuki Horiguchi, Takema Kato, Yasuko Shinkai, Hiromi Yamashita, Hyuga Yamada, Tomohiko Kawamura, Tsuyoshi Terada, Masaaki Okubo, Mitsuo Nagasaka, Yoshihito Nakagawa, Tomoyuki Shibata, Seiji Yamada, Makoto Urano, Tetsuya Tsukamoto, Hiroki Kurahashi, Makoto Kuroda, Naoki Ohmiya
    International journal of cancer 144(1) 80-88 2019年1月1日  査読有り
    Molecular irreversibleness with Helicobacter pylori (H. pylori) infection might have a role in gastric tumorigenesis after H. pylori eradication. We performed comprehensive DNA methylation profiling of gastric mucosa after H. pylori eradication with or without gastric cancer. Using four different groups of biopsies obtained from gastric body without history of H. pylori infection (Hp-), gastric body without cancer after H. pylori eradication (cancer-free body), gastric body with early gastric cancer diagnosed after H. pylori eradication (EGC body) and their paired samples from adjacent mucosa of cancer (EGC ADJ), methylation status of five candidate genes (MYOD1, SLC16A12, IGF2, RORA and PRDM5) was examined by the bisulfite pyrosequencing. An Infinium Methylation EPIC BeadChip array was also used to characterize the methylation status of greater than 850,000 CpG sites. The EGC ADJ group showed highest methylation levels of five candidate genes among the four groups of biopsies. In the gastric body (cancer-free body + EGC body), methylation levels were significantly decreased in patients with longer period after eradication, while such association was not observed in EGC ADJ group. Hyper methylated samples were associated with shorter telomere, an indicator for rapid cell turnover, and higher DNMT1 protein expression, an enzyme related to methyl transfer reaction. The genome-wide methylation analysis demonstrated strikingly higher methylation levels especially at CpG islands in the EGC ADJ group. Exclusively hypermethylated promoter CpG islands in the same group frequently coded zinc finger proteins. Our data show that DNA methylation accumulation is associated with molecular irreversibleness and gastric carcinogenesis after H. pylori eradication.
  • 伊藤 里美, 山田 勢至, 竹内 沙弥花, 川島 佳晃, 下山 玲子, 藤原 真紀, 須藤 健助, 平澤 浩, 中川 満, 酒井 康弘, 浦野 誠, 塚本 徹哉, 黒田 誠, 安倍 雅人
    日本臨床細胞学会雑誌 57(Suppl.2) 735-735 2018年10月  
  • 山田 勢至, 寺西 隆雄, 渡邉 定克, 村山 和宏, 大場 茂生, 山崎 達弥, 信澤 純人, 廣瀬 雄一, 横尾 英明, 安倍 雅人
    Brain Tumor Pathology 35(Suppl.) 169-169 2018年9月  
  • 島 寛太, 田原 沙佑美, 中川 満, 岡部 麻子, 山田 勢至, 塚本 徹哉, 浦野 誠, 黒田 誠
    日本小児血液・がん学会雑誌 55(1) 104-104 2018年6月  
  • 島 寛太, 浦野 誠, 中川 満, 田原 沙佑美, 岡部 麻子, 山田 勢至, 塚本 徹哉, 黒田 誠
    日本病理学会会誌 107(1) 373-373 2018年4月  
  • 中川 満, 島 寛太, 田原 沙佑美, 岡部 麻子, 山田 勢至, 浦野 誠, 塚本 徹哉, 黒田 誠
    日本病理学会会誌 107(1) 374-374 2018年4月  
  • 浦野 誠, 中川 満, 島 寛太, 田原 沙佑美, 岡部 麻子, 山田 勢至, 塚本 徹哉, 黒田 誠
    日本婦人科病理学会誌 8(2) 59-63 2017年12月  

主要なMISC

 27
  • Vanessa Y Ruiz, Corinne E Praska, Georgina Armstrong, Thomas M Kollmeyer, Seiji Yamada, Paul A Decker, Matthew L Kosel, Jeanette E Eckel-Passow, Daniel H Lachance, Matthew N Bainbridge, Beatrice S Melin, Melissa L Bondy, Robert B Jenkins
    Neuro-oncology 20(6) 810-817 2018年5月18日  査読有り
    Background: Single-gene mutation syndromes account for some familial glioma (FG); however, they make up only a small fraction of glioma families. Gliomas can be classified into 3 major molecular subtypes based on isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion. We hypothesized that the prevalence of molecular subtypes might differ in familial versus sporadic gliomas and that tumors in the same family should have the same molecular subtype. Methods: Participants in the FG study (Gliogene) provided samples for germline DNA analysis. Formalin-fixed, paraffin-embedded tumors were obtained from a subset of FG cases, and DNA was extracted. We analyzed tissue from 75 families, including 10 families containing a second affected family member. Copy number variation data were obtained using a first-generation Affymetrix molecular inversion probe (MIP) array. Results: Samples from 62 of 75 (83%) FG cases could be classified into the 3 subtypes. The prevalence of the molecular subtypes was: 30 (48%) IDH-wildtype, 21 (34%) IDH-mutant non-codeleted, and 11 (19%) IDH-mutant and 1p/19q codeleted. This distribution of molecular subtypes was not statistically different from that of sporadic gliomas (P = 0.54). Of 10 paired FG samples, molecular subtypes were concordant for 7 (κ = 0.59): 3 IDH-mutant non-codeleted, 2 IDH-wildtype, and 2 IDH-mutant and 1p/19q codeleted gliomas. Conclusions: Our data suggest that within individual families, patients develop gliomas of the same molecular subtype. However, we did not observe differences in the prevalence of the molecular subtypes in FG compared with sporadic gliomas. These observations provide further insight into the distribution of molecular subtypes in FG.
  • Rachael A Vaubel, Alissa A Caron, Seiji Yamada, Paul A Decker, Jeanette E Eckel Passow, Fausto J Rodriguez, Amulya A Nageswara Rao, Daniel Lachance, Ian Parney, Robert Jenkins, Caterina Giannini
    Brain pathology (Zurich, Switzerland) 28(2) 172-182 2018年3月  査読有り
    Pleomorphic xanthoastrocytoma (PXA) is a rare localized glioma characterized by frequent BRAF V600E mutation and CDKN2A/B deletion. We explored the association of copy-number variants (CNVs) with BRAF mutations, tumor grade, and patient survival in a cohort of 41 PXA patients using OncoScan chromosomal microarray. Primary resection specimens were available in 38 cases, including 24 PXA and 14 anaplastic PXA (A-PXA), 23 BRAF V600E mutant tumors (61%). CNVs were identified in all cases and most frequently involved chromosome 9 with homozygous CDKN2A/B deletion (n = 33, 87%), a higher proportion than previously detected by comparative genomic hybridization (50%-60%) (37). CDKN2A/B deletion was present in similar proportion of PXA (83%), A-PXA (93%), BRAF V600E (87%), and wild-type (87%) tumors. Whole chromosome gains/losses were frequent, including gains +7 (n = 15), +2 (n = 11), +5 (n = 10), +21 (n = 10), +20 (n = 9), +12 (n = 8), +15 (n = 8), and losses -22 (n = 11), -14 (n = 7), -13 (n = 5). Losses and copy-neutral loss of heterozygosity were significantly more common in A-PXA, involving chromosomes 22 (P = 0.009) and 14 (P = 0.03). Amplification of 8p and 12q was identified in a single tumor. Histologic grade was a robust predictor of overall survival (P = 0.003), while other copy-number changes, including CDKN2A/B deletion, did not show significant association with survival. Distinct histologic patterns of anaplasia included increased mitotic activity in an otherwise classic PXA or associated with small cell, fibrillary, or epithelioid morphology, with loss of SMARCB1 expression in one case. In 10 cases, matched specimens were compared, including A-PXA with areas of distinct low- and high-grade morphology (n = 2), matched primary/tumor recurrence (n = 7), or both (n = 1). Copy-number changes on recurrence/anaplastic transformation were complex and highly variable, from nearly identical profiles to numerous copy-number changes. Overall, we confirm CDKN2A/B deletion as key a feature of PXA not associated with tumor grade or BRAF mutation, but central to the underlying genetics of PXA.
  • Seiji Yamada, Tatsuya Yamazaki, Satoshi Nakata, Sumihito Nobusawa, Hayato Ikota, Munenori Ide, Kazuyuki Mizushima, Yasuo Harigaya, Junko Hirato, Hideaki Yokoo
    Neuropathology : official journal of the Japanese Society of Neuropathology 37(4) 335-340 2017年8月  査読有り筆頭著者責任著者
    Dentatorubral-pallidoluysian atrophy (DRPLA), one of the polyglutamine diseases, has not been reported in combination with ganglioglioma (GG). Herein, we report an autopsy case of a 72-year-old man with DRPLA with a small GG component harboring neurofibrillary tangles (NFTs) and polyglutamine aggregates. NFTs, cytoplasmic accumulations of hyper-phosphorylated tau, are mainly observed in Alzheimer's disease (AD) and other tau-associated neurodegenerative disorders. NFTs can also be present in normal aging, and are occasionally observed in low-grade central nervous system (CNS) neoplasms such as GG. In the present case, whole brain examination demonstrated widespread deposition of polyglutamine aggregates, including GG, whereas NFTs were restricted to the GG component. In addition, no other AD or aging-related neuropathological structures were detected throughout the CNS. These findings may provide us with clues to elucidate the pathogenetic mechanisms that neuronal neoplasms may have to develop NFTs regardless of aging, and that polyglutamine may accumulate in neoplastic neurons in polyglutamine disease.
  • Seiji Yamada, Christopher P Wood, Jawad A Shah, Jonathan Vida, Joseph E Parisi, Mark E Jentoft
    Neuropathology : official journal of the Japanese Society of Neuropathology 36(5) 480-484 2016年10月  査読有り筆頭著者
    Hypothalamic hamartomas are rare tumors that typically present in childhood, often with gelastic seizures, precocious puberty, or as a manifestation of Pallister-Hall syndrome. Neurofibrillary tangles are cytoplasmic aggregates of hyperphosphorylated tau that are best recognized in Alzheimer disease, other tau-associated neurodegenerative diseases, or as part of aging, but occasionally may be seen in low-grade neoplasms with a ganglion cell component as gangliocytoma or ganglioglioma. Herein, we report a case of hypothalamic hamartoma with neurofibrillary tangles.
  • Seiji Yamada, Benjamin R Kipp, Jesse S Voss, Caterina Giannini, Aditya Raghunathan
    The American journal of surgical pathology 40(2) 279-84 2016年2月  査読有り筆頭著者
    Pleomorphic xanthoastrocytoma (PXA) has rarely been reported in combination with infiltrating glioma, historically interpreted as a "collision tumor." Isocitrate dehydrogenase 1 (IDH1) and BRAF V600E mutations are usually not concurrent. The former is typical of adult infiltrating gliomas, and the latter is identified in a variety of primary central nervous system neoplasms, including PXA, ganglioglioma, pilocytic astrocytoma, and rarely infiltrating gliomas. We report the case of a 56-year-old man presenting with seizures and headaches. Magnetic resonance imaging revealed a large right temporal lobe mass with low T1 and high T2/FLAIR signal and a discrete contrast-enhancing focus. Histologically, the tumor showed 2 distinct components: an infiltrating astrocytoma harboring 5 mitoses/10 high-power fields and a relatively circumscribed focus, resembling PXA with, at most, 2 mitoses/10 high-power fields. No microvascular proliferation or necrosis was present in either component. The infiltrating astrocytoma component contained numerous axons, whereas the PXA-like component had sparse axons, as demonstrated by the neurofilament immunostain. Both components were positive for the mutant IDH1 R132H and showed loss of ATRX expression, whereas BRAF V600E was restricted to the PXA-like component. On sequencing of the 2 components separately after microdissection, both showed identical IDH1 R132H and TP53 R273C point mutations, whereas the BRAF V600E mutation was limited to the PXA-like component. These findings are consistent with clonal expansion of a morphologically distinct focus, harboring a private BRAF V600E mutation within an IDH1-mutant glioma. Intratumoral heterogeneity and clonal evolution, as seems to have occurred here, suggest reevaluation of "collision tumors" as a concept.
  • Seiji Yamada, Benjamin Kipp, Jesse Voss, Caterina Giannini, Aditya Raghunathan
    JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY 74(6) 607-607 2015年6月  
  • 山田勢至, 大喜多賢治, 櫻井圭太, 松川則之, 稲垣宏, 吉田眞理
    診断病理 31(1) 19-24 2014年  査読有り
    血清アクアポリン4抗体陽性で、延髄から上位頸髄に脱髄病変を有する50代男性のNMOSDの1剖検例を経験した。比較的急激に症状が進行し、8ヵ月の全経過中に視神経炎の所見を呈さなかった。組織像は脱髄所見およびアクアポリン4の染色性が低下していたことに加え、GFAP染色性の低下を示すアストロサイト傷害像を認め、NMOSDとして矛盾しないものであった。視神経障害がなく脊髄障害のみを呈する症例は比較的稀であり、診断に苦慮することがある。病理所見に若干の文献的考察を加えて報告する。(著者抄録)
  • Seiji Yamada, Fumihiko Sato, Hongjing Xia, Hisashi Takino, Satoru Kominato, Masaki Ri, Takashi Ishida, Shinsuke Iida, Hiroshi Inagaki, Kazuo Yamada
    Human pathology 43(8) 1322-7 2012年8月  査読有り筆頭著者
    Forkhead box P1 protein is a transcription factor involved in cell signaling and regulation of gene expression and is essential for B-cell development. Forkhead box P1 overexpression has been associated with a worsened prognosis in some B-cell lymphomas. However, little is known about the clinicopathologic significance of forkhead box P1 in T-cell malignancies. In this study, immunohistochemistry for forkhead box P1 was performed in peripheral T-cell lymphoma, not otherwise specified, cases (n = 41), which were then divided into lower (n = 15) and higher (n = 26) forkhead box P1 expressers. Results of real-time quantitative reverse transcriptase polymerase chain reaction for forkhead box P1 messenger RNA supported the data on immunohistochemical forkhead box P1 expression. Forkhead box P1 overexpression in lymphoma cells was inversely associated with proliferation activity as evaluated by Ki-67 expression. Double immunostain for forkhead box P1 and a T-cell marker in normal lymph nodes showed forkhead box P1 signals in many of nonneoplastic T cells. Prognostic analysis showed that forkhead box P1 overexpression was associated with an improved overall survival of the patients with peripheral T-cell lymphoma, not otherwise specified, and was independent of the International Prognostic Index in multivariate analysis. Forkhead box P1 overexpression may be associated with less activated phenotype of the tumors and with a better prognosis in patients with peripheral T-cell lymphoma, not otherwise specified. The clinicopathologic significance of forkhead box P1 overexpression in peripheral T-cell lymphoma, not otherwise specified, may be different from that in B-cell lymphomas.
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