Primary large B-cell lymphoma of the central nervous system: A reappraisal of CD5-positive cases based on clinical, pathological, and molecular evaluation.

Seiji Yamada, Akira Satou, Yuta Tsuyuki, Sachiko Iba, Yuka Okumura, Eri Ishikawa, Hideaki Ito, Yasunori Kogure, Naoe Goto, Motoki Tanikawa, Kazuyuki Shimada, Tetsuya Tsukamoto, Kennosuke Karube, Hideaki Yokoo, Keisuke Kataoka, Akihiro Tomita, Mitsuhito Mase, Shigeo Nakamura

Pathology international 2024年12月11日査読有り筆頭著者責任著者

CD5 expression is seen in 5%-10% of de novo diffuse large B-cell lymphomas (DLBCLs). Primary large B-cell lymphoma of the central nervous system (PCNS-LBCL) also exhibits CD5 expression in a minority of cases, however, clinicopathological and molecular features remain largely unclarified. Here we present the clinical, molecular, and pathological features of 11 CD5-positive (+) PCNS-LBCL cases, occupying 6.7% of all 165 PCNS-LBCLs diagnosed in our institutions. While CD5+ systemic DLBCL has been recognized as a distinctive subgroup showing an aggressive clinical course, no obvious differences were found between CD5+ and CD5-negative subgroups among the present CNS patients clinically. MYD88 p.L265P and CD79B p.Y196 mutations were detected in eight (73%) and seven (64%) cases, respectively, supporting previous reports. Notably, the microenvironmental immune cells were universally PD-L1/CD274-positive, and the higher levels tended to present favorable overall survival, as already evidenced in the PCNS-LBCL series. In contrast, neoplastic PD-L1/CD274 expression was undetectable in all cases. Indeed, no structural variations or copy number alterations involving PD-1 ligands were detected by targeted-capture sequencing and fluorescence in situ hybridization. While further studies are warranted, we may have confirmed similarity between PCNS-LBCLs and intravascular large B-cell lymphomas from a molecular standpoint.
Chromogenic in situ hybridization reveals specific expression pattern of long non-coding RNA DRAIC in formalin-fixed paraffin-embedded specimen

Kouhei Sakurai, Seiji Yamada, Rika Ito, Mako Ochiai, Tatsuya Ando, Yasuhiro Sakai, Taku Kato, Hiroyasu Ito

Non-coding RNA Research 9(1) 76-83 2024年3月査読有り責任著者
SEGA-like circumscribed astrocytoma in a non-NF1 patient, harboring molecular profile of GBM. A case report.

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.
DNA methylation array analysis for diffuse leptomeningeal glioneuronal tumor with conspicuous hypothalamic mass. A case report

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
Primary central nervous system lymphomas with massive intratumoral hemorrhage: Clinical, radiological, pathological, and molecular features of six cases.

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.
Primary spinal intramedullary Ewing-like sarcoma harboring CIC-DUX4 translocation: a similar cytological appearance as its soft tissue counterpart but no lobulation in association with desmoplastic stroma.

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.
An epilepsy-associated glioneuronal tumor with mixed morphology harboring FGFR1 mutation.

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.

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主要なMISC

Molecular subtyping of tumors from patients with familial glioma.

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.
Recurrent copy number alterations in low-grade and anaplastic pleomorphic xanthoastrocytoma with and without BRAF V600E mutation.

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
Dentatorubral-pallidoluysian atrophy (DRPLA) with a small ganglioglioma component containing neurofibrillary tangles and polyglutamine aggregation.

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
Hypothalamic hamartoma with neurofibrillary tangles.

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
Combined "Infiltrating Astrocytoma/Pleomorphic Xanthoastrocytoma" Harboring IDH1 R132H and BRAF V600E Mutations.

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
Combined IDH1-R132H Mutant "Infiltrating Astrocytoma/Pleomorphic Xanthoastrocytoma'' With Concurrent BRAF V600E Mutation

Seiji Yamada, Benjamin Kipp, Jesse Voss, Caterina Giannini, Aditya Raghunathan

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY 74(6) 607-607 2015年6月
視神経炎を呈さなかった視神経脊髄炎類縁疾患（neuromyelitis optica spectrum disorders:NMOSD）の1剖検例

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年査読有り筆頭著者責任著者
Forkhead box P1 overexpression and its clinicopathologic significance in peripheral T-cell lymphoma, not otherwise specified.

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

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脳腫瘍臨床病理カラーアトラス

山田勢至 (担当:分担執筆, 範囲:びまん髄膜性グリア神経細胞腫瘍、中枢性神経細胞腫、脳室外神経細胞腫、小脳脂肪神経細胞腫)

医学書院 2024年5月 (ISBN: 9784260053297)
病理と臨床臨時増刊号「病理形態学キーワード2024」

山田勢至 (担当:分担執筆, 範囲:びまん性グリオーマと限局性グリオーマ、微小血管増殖およびグリオーマでみられるその他の血管の異常、胎児性腫瘍といわゆるPNET様要素、oligodendroglia-like cell (OLC)、ロゼットおよび偽ロゼット、BRAF異常を示す脳腫瘍)

文光堂 2024年3月
腫瘍病理鑑別診断アトラス脳腫瘍第2版

山田勢至 (担当:分担執筆, 範囲:グリア神経細胞系および神経細胞系腫瘍)

文光堂 2024年2月 (ISBN: 9784830622700)
日本臨牀増刊号臨床脳腫瘍学

山田勢至 (担当:分担執筆, 範囲:胚細胞性腫瘍)

2023年12月
画像で学ぶ病理の正常像と疾患像 6．神経疾患（脳） MEDICAL TECHNOLOGY 50巻3号

医師薬出版 2022年3月
臨床医のための神経病理再入門「孤立性線維性腫瘍・血管周皮腫」 Clinical Neuroscience Vol.38 No.2

山田勢至

中外医薬社 2020年2月
放射線科医も知っておくべき免疫染色検査診断や治療に有用な免疫染色マーカー臨床画像 Vol.35

山田勢至

メジカルビュー社 2019年3月
臨床医のための神経病理再入門「上衣」 Clinical Neuroscience Vol.36 No.4

山田勢至, 横尾英明 (担当:分担執筆)

中外医薬社 2018年4月
病理と臨床臨時増刊号「病理診断に直結した組織学」

山田勢至, 横尾英明 (担当:分担執筆, 範囲:中枢神経)

文光堂 2017年
脳腫瘍臨床病理カラーアトラス第4版

山田勢至, 荒川芳輝, 平戸純子 (担当:分担執筆, 範囲:Diffuse leptomeningeal glioneuronal tumor)

医学書院 2017年
粘膜関連リンパ組織型辺縁帯リンパ腫(MALTリンパ腫) 病理と臨床28巻7号

稲垣宏, 山田勢至, 滝野寿 (担当:分担執筆)

文光堂 2010年