Faculty Profiles - akihide Tanimoto

Papers - akihide Tanimoto

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内田裕之, 赤羽俊章, 比嘉那優大, 米澤大, 霧島茉莉, 谷本昭英, 吉本幸司 . Lower-grade gliomaの遺伝子プロファイル診断と予後についての検討 . Brain Tumor Pathology38 ( Suppl. ) 077 - 077 2021.5

Takashi Tasaki, Kazuhito Hatanaka, Ikumi Kitazono, Hirotsugu Noguchi, Kazuhiro Tabata, Michiyo Higashi, Kouki Maeda, Tomoyuki Yokose, Toshimasa Uekusa, Akihide Tanimoto . Pulmonary infarction caused by sarcoidosis vascular involvement: A case report. . Pathology international71 ( 7 ) 480 - 484 2021.4Reviewed International journal

Language：English

Sarcoidosis is a systemic granulomatous disease. In pulmonary sarcoidosis, granulomatous vascular involvement is a common feature that occurs in all types of vessels, including large elastic arteries to venules, but sarcoidosis complicated with pulmonary infarction has not been reported. We report a case of a 60 years old female, who was operated on a clinical diagnosis of lung cancer, and histological examination revealed a pulmonary infarction and sarcoidosis. In the pulmonary elastic arteries, granulomas infiltrated the adventitia and media, and caused elastic fiber collapse and destruction. Arterial occlusion by granulomas was observed in the edge of the infarcted area. It was considered that the arterial sarcoidosis granuloma involvement was the cause of pulmonary infarction. Sarcoidosis is a significant risk factor for cardiovascular events. However, pulmonary infarction is an extremely rare complication of sarcoidosis. Our case suggests that sarcoidosis may cause vascular events in the lungs.

DOI： 10.1111/pin.13104

Hirotsugu Noguchi, Michiyo Higashi, Tetsuya Idichi, Hiroshi Kurahara, Yuko Mataki, Takashi Tasaki, Ikumi Kitazono, Takao Ohtsuka, Akihide Tanimoto . Rare histological subtype of invasive micropapillary carcinoma in the ampulla of Vater: A case report. . World journal of clinical cases9 ( 11 ) 2671 - 2678 2021.4Reviewed International journal

Language：English

BACKGROUND: Carcinoma of the ampulla of Vater is an uncommon ampullo-pancreatobiliary neoplasm, and the most common histological type is adenocarcinoma with a tubular growth pattern. Invasive micropapillary carcinoma (IMPC) is an aggressive variant of adenocarcinoma in several organs that is associated with lymph node metastasis and poor prognosis. IMPC was first described as a histological subtype of breast cancer; however, IMPC of the ampulla of Vater is extremely rare, with only three articles reported in the English literature. CASE SUMMARY: We have reported a case of IMPC of the ampulla of Vater in an 80-year-old man. Microscopically, the surface area of the carcinoma was composed of tubulopapillary structures mimicking intra-ampullary papillary-tubular neoplasm, and the deep invasive front area exhibited a pattern of IMPC. The carcinoma showed lymphatic invasion and extensive lymph node metastasis. The immunohistochemical study revealed mixed intestinal and gastric/pan-creatobiliary phenotypes. CONCLUSION: This rare subtype tumor in the ampulla of Vater showed a histologically mixed phenotype and exhibited aggressive behavior.

DOI： 10.12998/wjcc.v9.i11.2671

Ikumi Kitazono, Toshiaki Akahane, Mika Sakihama, Shintaro Yanazume, Michiko Matsushita, Kazuhiro Tabata, Yusuke Kobayashi, Hiroaki Kobayashi, Yoshihisa Umekita, Akihide Tanimoto . Human Papilloma Virus 18-Positive Submucosal Small Cell Neuroendocrine Carcinoma of the Vagina: An Immunohistochemical and Genomic Study. . International journal of surgical pathology29 ( 8 ) 10668969211007569 - 10668969211007569 2021.4Reviewed International journal

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

Primary vaginal neuroendocrine carcinoma (NEC) is extremely rare among female genital tract tumors. Here, we report 2 cases of vaginal small cell NEC (SCNEC) using immunohistochemistry and next-generation sequencing (NGS) analysis. The 2 patients were in their mid-to-late 70s, presented with abnormal vaginal bleeding and had a vaginal submucosal mass. The biopsied or resected tumors showed a typical neuroendocrine morphology consisting of solid nests of atypical tumor cells, with no specific organoid patterns, and proliferating in the vaginal submucosa. Immunohistochemical analysis showed strong and diffuse expression of chromogranin A, synaptophysin, and p16, but no thyroid transcription factor 1 expression. Additionally, both cases were positive for human papillomavirus (HPV) 18. An NGS-based cancer panel analysis revealed that the tumors carried NF1 and AR mutations, but no major driver mutations were detected. The results of this study suggested that HPV18 infection is linked to vaginal SCNEC.

DOI： 10.1177/10668969211007569

MOE IJIRI, YU-CHANG LAI, HIROAKI KAWAGUCHI, YOSHIKAZU FUJIMOTO, NAOKI MIURA, TOMOHIDE MATSUO, AKIHIDE TANIMOTO . NR6A1 Allelic Frequencies as an Index for both Miniaturizing and Increasing Pig Body Size . In Vivo35 ( 1 ) 163 - 167 2021.1Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：Anticancer Research USA Inc.

Background/Aim: The number of vertebrae in swine varies from 19 to 23 and is associated with body size. Nuclear receptor subfamily 6 group A member 1 (NR6A1) is considered a strong candidate for affecting the number of vertebrae in swine. Wild boars, which uniformly have 19 vertebrae, have the wild type allele while multi-vertebrae European commercial pigs have the mutated allele. Our aim was to confirm the factor of the miniaturization. Materials and Methods: We examined vertebrae number and NR6A1 polymorphism in the Microminipig and three domestic breeds that vary in body size. Results: The Microminipig had 19 or less vertebrae and a wild type NR6A1 genotype. Three domestic breeds had more than 21 vertebrae while the largest vertebrae number was observed in multi-vertebrae-fixed Large White. Heterozygous genotypes were observed in the middle-sized indigenous pig while homozygous NR6A1 mutations were observed in European commercial breeds. Conclusion: NR6A1 could be a useful index for both miniaturizing and increasing pig body size.

DOI： 10.21873/invivo.12244

Yusuke Kobayashi, Ikumi Kitazono, Toshiaki Akahane, Shintaro Yanazume, Masaki Kamio, Shinichi Togami, Sachio Nohara, Ippei Sakamoto, Seiya Yokoyama, Kazuhiro Tabata, Hiroaki Kobayashi, Akihide Tanimoto . Molecular Evaluation of Endometrial Dedifferentiated Carcinoma, Endometrioid Carcinoma, Carcinosarcoma, and Serous Carcinoma Using a Custom-Made Small Cancer Panel. . Pathology oncology research : POR27 1610013 - 1610013 2021Reviewed International journal

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

It is often difficult to histologically differentiate among endometrial dedifferentiated carcinoma (DC), endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma (CS) due to the presence of solid components. In this study, we aimed to categorize these carcinomas according to The Cancer Genome Atlas (TCGA) classification using a small custom-made cancer genome panel (56 genes and 17 microsatellite regions) for integrated molecular diagnosis. A total of 36 endometrial cancer cases with solid components were assessed using IHC, next-generation sequencing (NGS), and the custom-made panel. Among 19 EC cases, six were categorized as MMR-deficient (MMR-d) and eight were classified as having a nonspecific molecular profile. Three EC cases were classified as POLE mutation (POLEmut)-type, which had a very high tumor mutation burden (TMB) and low microsatellite instability (MSI). Increased TMB and MSI were observed in all three DC cases, classified as MMR-d with mutations in MLH1 and POLD1. Except for one case classified as MMR-d, all SC cases exhibited TP53 mutations and were classified as p53 mutation-type. SC cases also exhibited amplification of CCND1, CCNE1, and MYC. CS cases were classified as three TCGA types other than the POLEmut-type. The IHC results for p53 and ARID1A were almost consistent with their mutation status. NGS analysis using a small panel enables categorization of endometrial cancers with solid proliferation according to TCGA classification. As TCGA molecular classification does not consider histological findings, an integrated analytical procedure including IHC and NGS may be a practical diagnostic tool for endometrial cancers.

DOI： 10.3389/pore.2021.1610013

HAYASHI Tomomi, KADONO Jun, INOUE Maki, SAKAMOTO Akihiko, HUTAWATARI Hisatomo, HIRAKI Tsubasa, TANIMOTO Akihide, FUROI Akira . Evaluation of Hepatic Functional Reserve and Perioperative Course after Hepatectomy in a Case of Dubin-Johnson Syndrome . Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association)82 ( 12 ) 2262 - 2269 2021Reviewed

Language：Japanese Publisher：Japan Surgical Association

<p>A case of hepatocellular carcinoma in a patient with Dubin-Johnson syndrome (DJS) focusing on evaluation of hepatic functional reserve and the perioperative clinical course is presented.</p><p>A 66-year-old man with a medical history of DJS and diabetes mellitus was diagnosed with hepatocellular carcinoma (HCC) when he had a rickettsial infection. The preoperative liver function tests showed an increased bilirubin level (total 4.6, direct 3.4 mg/dl), and normal PT (92%) and albumin (4.2 g/dl) levels without ascites or encephalopathy. The Child-Pugh score was B (7). The ICGR<sub>15</sub> level was 11%. The LHL<sub>15</sub> value of the GSA scintigram was almost normal (0.909). S4 segmentectomy and S2 partial resection were performed uneventfully except for transient elevation of the T-Bil level that recovered to the preoperative level on the 28<sup>th</sup> postoperative day. DJS was confirmed on histopathological examination. Both the ICG test and the GSA scintigram evaluated hepatic functional reserve accurately. Inchin-ko-to may be effective for hyperbilirubinemia after hepatectomy in DJS cases.</p>

DOI： 10.3919/jjsa.82.2262

Yuto Hozaka, Yuko Mataki, Hiroshi Kurahara, Kiyonori Tanoue, Tetsuya Idichi, Yota Kawasaki, Satoshi Iino, Pramod Nepal, Takaaki Arigami, Kosei Maemura, Hirotsugu Noguchi, Hiroyuki Shinchi, Akihide Tanimoto, Shoji Natsugoe, Takao Ohtsuka . Usefulness of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography in primary cystadenocarcinoma of the mesentery: a case report. . Surgical case reports6 ( 1 ) 306 - 306 2020.12Reviewed International journal

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

BACKGROUND: Mesenteric cysts have various histological forms, including mesenteric cystadenomas and borderline cystic neoplasms. Primary cystadenocarcinoma of the mesentery is extremely rare; therefore, the clinical and radiological features of this tumor have not been fully elucidated. CASE PRESENTATION: A 50-year-old Japanese woman had a complaint of a left-sided abdominal distention. Enhanced computed tomography and magnetic resonance imaging revealed a unilocular cystic lesion measuring approximately 10 cm located in the left side of the abdomen. 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) revealed mottled mild FDG uptake in the cyst wall and intense FDG uptake in several mural nodules. The cystic mass with the descending colon was completely removed. Pathological examination of the specimens revealed various histologic patterns of adenocarcinoma, including mucin production in the mural nodules. We eventually diagnosed a primary cystadenocarcinoma arising from the mesentery of the descending colon. CONCLUSIONS: Malignancy should be suspected in mesenteric or retroperitoneal cystic tumors with high FDG uptake, and complete resection should be performed with adequate margins.

DOI： 10.1186/s40792-020-01079-2

Ikumi Kitazono, Taiji Hamada, Takuya Yoshimura, Mari Kirishima, Seiya Yokoyama, Toshiaki Akahane, Akihide Tanimoto . PCP4/PEP19 downregulates neurite outgrowth via transcriptional regulation of Ascl1 and NeuroD1 expression in human neuroblastoma M17 cells. . Laboratory investigation; a journal of technical methods and pathology100 ( 12 ) 1551 - 1563 2020.12Reviewed International journal

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

Purkinje cell protein 4/peptide 19 (PCP4/PEP19) is 7.6 kDa peptide originally found in Purkinje cells. PCP4/PEP19 is a differentiation maker of Purkinje cells, where it functions as an antiapoptotic factor. Cerebral neuronal cells also express PCP4/PEP19, which may be related to neuronal cell survival. However, evidence suggests that PCP4/PEP19 may also be involved in neuronal differentiation. Here, we investigated the effects of PCP4/PEP19 expression on neuronal differentiation by analyzing neurite outgrowth, and expression of neuronal differentiation markers in cultured human neuroblastoma M17 cells. When PCP4/PEP19 expression was reduced by siRNA-mediated knockdown, neurite outgrowth was significantly increased. Among many differentiation markers tested, expression of NeuroD1 was increased, while that of Ascl1 was decreased upon PCP4/PEP19 knockdown. Furthermore, luciferase reporter assays revealed that PCP4/PEP19 knockdown upregulated NeuroD1 and downregulated Ascl1 expression, at the transcriptional level. These results suggest a new function of PCP4/PEP19, which suppresses neurite outgrowth and neuronal differentiation through the regulation of NeuroD1 and Ascl1 expression in M17 cells. Furthermore, immunohistochemical studies showed that PCP4/PEP19 localizes in the nuclei of human neuroblastoma cells. Therefore, PCP4/PEP19 may also be an intranuclear negative regulator of neuronal differentiation and may thus be a potential therapeutic target to promote cellular differentiation in human neuroblastoma.

DOI： 10.1038/s41374-020-0462-z

Hozaka Yuto, Mataki Yuko, Kurahara Hiroshi, Tanoue Kiyonori, Idichi Tetsuya, Kawasaki Yota, Iino Satoshi, Nepal Pramod, Arigami Takaaki, Maemura Kosei, Noguchi Hirotsugu, Shinchi Hiroyuki, Tanimoto Akihide, Natsugoe Shoji, Ohtsuka Takao . 腸間膜の原発性嚢胞腺癌における18F-フルオロデオキシグルコース-PET/CT検査の有用性　1症例報告(Usefulness of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography in primary cystadenocarcinoma of the mesentery: a case report) . Surgical Case Reports6 1 of 8 - 8 of 8 2020.12Reviewed

Language：English Publisher：Springer Berlin Heidelberg

左腹部膨満を主訴とする50歳日本人女性症例について検討した。増強CT検査およびMRI検査では左腹部に約10cmの単房性嚢胞性病変を認めた。18F-フルオロデオキシグルコース(FDG)-PET/CT検査では、嚢胞壁に斑点状のFDG軽度取り込みを認め、いくつかの壁在性結節に強度FDG取り込みを認めた。嚢胞性腫瘤は下行結腸とともに完全に切除した。検体の病理検査では腺癌の様々な組織学的パターンを認め、その中に壁在性結節におけるムチン産生も含まれた。最終診断は下行結腸の腸間膜から生じた原発性嚢胞腺癌であった。

Tomomi Yamaguchi, Toshiaki Akahane, Ohi Harada, Yasutaka Kato, Eriko Aimono, Hidehiro Takei, Takashi Tasaki, Hirotsugu Noguchi, Hiroshi Nishihara, Hajime Kamata, Akihide Tanimoto . Next-generation sequencing in residual liquid-based cytology specimens for cancer genome analysis. . Diagnostic cytopathology48 ( 11 ) 965 - 971 2020.11Reviewed International journal

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

BACKGROUND: Cancer genome profiling of cytology specimens using next-generation sequencing (NGS) requires adequate and good-quality DNA. Genomic examination of cytology samples was conventionally performed on cell block (CB) or smear specimens than on residual liquid-based cytology (LBC) specimens, which are high-quality DNA sources even after long-term storage. METHODS: We estimated tumor fractions of 37 residual LBC specimens, including 30 fine needle aspiration (FNA) samples from the thyroid (12 papillary thyroid carcinomas and two malignant lymphomas), lymph node (13 metastatic carcinomas and one malignant lymphoma), and breast cancer (one phyllodes tumor and one invasive ductal carcinoma), two pancreatic carcinoma samples, and five liquid (ascites, pleural effusion, and cerebrospinal fluid) samples. The DNA was extracted from all samples and subjected to NGS using a customized cancer gene panel comprising 28 cancer-related genes. RESULTS: NGS analysis revealed somatic mutations corresponding to pathological diagnosis with adequate variant allele frequency (VAF) in 24 LBC specimens, which had significantly higher tumor fraction (72.5% ± 4.9%). Ten cases, including the five fluid samples, had very small tumor fractions (7.5% ± 2.3%) to obtain sufficient VAF. Other two samples had high tumor fractions but showed very low VAF, indicating the presence of fusion genes. The remaining one sample yielded no DNA recovery. CONCLUSION: The residual LBC specimens collected by FNA from the thyroid gland and lymph node were verified to carry high tumor fraction and could serve as an alternate source for molecular testing to screen and diagnose cancers without the use of CB or smears.

DOI： 10.1002/dc.24511

東美智代, 横山勢也, 米澤傑, 谷本昭英 . 【IPMN大全】IPMNの歴史的変遷 IPMNにおけるMUC発現とその評価の歴史 . 胆と膵41 ( 臨増特大 ) 1159 - 1162 2020.11Reviewed

Language：Japanese Publisher：医学図書出版(株)

膵管内乳頭粘液性腫瘍(intraductal papillary mucinous neoplasm:IPMN)の大きな特徴は「粘液の産生」である。ムチンは「粘液」の主成分であり、細胞の保護を行い恒常性維持に大きな役目を果たしている。ムチンの骨格であるコア蛋白が「MUC」という総称でよばれており、クローニングされた順に番号が付いている。IPMNは亜型によってMUCの発現形式が異なっていることは現在ではよく知られている。しかし、IPMNが認識されはじめた当初はMUC2(+)の症例がほとんどであった。症例数の蓄積とともにMUC2(-)の症例が認識され、臨床病理学的特徴も大きく異なることがわかり、2004年頃に亜型として確立された。MUC発現は亜型のみでなく予後などの悪性度とも関連しており、早期診断などへの臨床応用も期待される。(著者抄録)

Daiki Yoshii, Takenobu Nakagawa, Yoshihiro Komohara, Hiroaki Kawaguchi, Sohsuke Yamada, Akihide Tanimoto . Phenotypic Changes in Macrophage Activation in a Model of Nonalcoholic Fatty Liver Disease using Microminipigs. . Journal of atherosclerosis and thrombosis28 ( 8 ) 844 - 851 2020.10Reviewed

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Atherosclerosis Society

AIM: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders associated with metabolic syndrome, and its prevalence has been on the rise. The pathogenesis of NAFLD has not yet been sufficiently elucidated due to the multifactorial nature of the disease, although the activation of macrophages/Kupffer cells is considered to be involved. We previously reported an animal model of NAFLD using MicrominipigsTM (µMPs) fed high-fat diets containing cholesterol with or without cholic acid. The aim of this study was to investigate the phenotypic changes of macrophages that occur during the development of NAFLD. METHODS: Immunohistochemistry of macrophages, lymphocytes, and stellate cells was performed using liver samples, and the density of positive cells was analyzed. RESULTS: The number of Iba-1-positive macrophages increased with increasing cholesterol content in the diet. The numbers of CD163-positive macrophages and CD204-positive macrophages also increased with increasing cholesterol content in the diet; however, the proportion of CD204-positive macrophages among Iba-1-positive macrophages was significantly reduced by cholic acid supplementation. CONCLUSION: The results suggest that lipid accumulation induced macrophage recruitment in swine livers, and that the number of M2-like macrophages increased at the early stage of NAFLD, while the number of M1-like macrophages increased at the late stage of NAFLD, resulting in a liver condition like non-alcoholic steatohepatitis. We provide evidence of the phenotypic changes that occur in macrophages during the development of NAFLD that has never been reported before using µMPs.

DOI： 10.5551/jat.57703

Toshiaki Akahane, Naoki Kanomata, Oi Harada, Tetsumasa Yamashita, Junichi Kurebayashi, Akihide Tanimoto, Takuya Moriya . Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions. . BMC cancer20 ( 1 ) 944 - 944 2020.10Reviewed International journal

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

BACKGROUND: Next-generation sequencing (NGS) has shown that recurrent/metastatic breast cancer lesions may have additional genetic changes compared with the primary tumor. These additional changes may be related to tumor progression and/or drug resistance. However, breast cancer-targeted NGS is not still widely used in clinical practice to compare the genomic profiles of primary breast cancer and recurrent/metastatic lesions. METHODS: Triplet samples of genomic DNA were extracted from each patient's normal breast tissue, primary breast cancer, and recurrent/metastatic lesion(s). A DNA library was constructed using the QIAseq Human Breast Cancer Panel (93 genes, Qiagen) and then sequenced using MiSeq (Illumina). The Qiagen web portal was utilized for data analysis. RESULTS: Successful results for three or four samples (normal breast tissue, primary tumor, and at least one metastatic/recurrent lesion) were obtained for 11 of 35 breast cancer patients with recurrence/metastases (36 samples). We detected shared somatic mutations in all but one patient, who had a germline mutation in TP53. Additional mutations that were detected in recurrent/metastatic lesions compared with primary tumor were in genes including TP53 (three patients) and one case each of ATR, BLM, CBFB, EP300, ERBB2, MUC16, PBRM1, and PIK3CA. Actionable mutations and/or copy number variations (CNVs) were detected in 73% (8/11) of recurrent/metastatic breast cancer lesions. CONCLUSIONS: The QIAseq Human Breast Cancer Panel assay showed that recurrent/metastatic breast cancers sometimes acquired additional mutations and CNV. Such additional genomic changes could provide therapeutic target.

DOI： 10.1186/s12885-020-07432-w

Nayuta Higa, Toshiaki Akahane, Seiya Yokoyama, Hajime Yonezawa, Hiroyuki Uchida, Tomoko Takajo, Mari Kirishima, Taiji Hamada, Kei Matsuo, Shingo Fujio, Tomoko Hanada, Hiroshi Hosoyama, Masanori Yonenaga, Akihisa Sakamoto, Tsubasa Hiraki, Akihide Tanimoto, Koji Yoshimoto . A tailored next-generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas. . Cancer science111 ( 10 ) 3902 - 3911 2020.10

Central nervous system tumors are classified based on an integrated diagnosis combining histology and molecular characteristics, including IDH1/2 and H3-K27M mutations, as well as 1p/19q codeletion. Here, we aimed to develop and assess the feasibility of a glioma-tailored 48-gene next-generation sequencing (NGS) panel for integrated glioma diagnosis. We designed a glioma-tailored 48-gene NGS panel for detecting 1p/19q codeletion and mutations in IDH1/2, TP53, PTEN, PDGFRA, NF1, RB1, CDKN2A/B, CDK4, and the TERT promoter (TERTp). We analyzed 106 glioma patients (grade II: 19 cases, grade III: 23 cases, grade IV: 64 cases) using this system. The 1p/19q codeletion was detected precisely in oligodendroglial tumors using our NGS panel. In a cohort of 64 grade Ⅳ gliomas, we identified 56 IDH-wildtype glioblastomas. Within these IDH-wildtype glioblastomas, 33 samples (58.9%) showed a mutation in TERTp. Notably, PDGFRA mutations and their amplification were more commonly seen in TERTp-wildtype glioblastomas (43%) than in TERTp-mutant glioblastomas (6%) (P = .001). Hierarchical molecular classification of IDH-wildtype glioblastomas revealed 3 distinct groups of IDH-wildtype glioblastomas. One major cluster was characterized by mutations in PDGFRA, amplification of CDK4 and PDGFRA, homozygous deletion of CDKN2A/B, and absence of TERTp mutations. This cluster was significantly associated with older age (P = .021), higher Ki-67 score (P = .007), poor prognosis (P = .012), and a periventricular tumor location. We report the development of a glioma-tailored NGS panel for detecting 1p/19q codeletion and driver gene mutations on a single platform. Our panel identified distinct subtypes of IDH- and TERTp-wildtype glioblastomas with frequent PDGFRA alterations.

DOI： 10.1111/cas.14597

Higa Nayuta, Akahane Toshiaki, Yokoyama Seiya, Yonezawa Hajime, Uchida Hiroyuki, Takajo Tomoko, Kirishima Mari, Hamada Taiji, Matsuo Kei, Fujio Shingo, Hanada Tomoko, Hosoyama Hiroshi, Yonenaga Masanori, Sakamoto Akihisa, Hiraki Tsubasa, Tanimoto Akihide, Yoshimoto Koji . 次世代シークエンサー用カスタム遺伝子パネルにより、野生型IDH変異およびTERTプロモーター領域に変異を有する膠芽腫の各サブタイプが同定される(A tailored next-generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas) . Cancer Science111 ( 10 ) 3902 - 3911 2020.10Reviewed

Language：English Publisher：John Wiley & Sons Australia, Ltd

今回、神経膠腫の分子病理学的統合診断を目的として、新たに48遺伝子で構成された次世代シークエンサー(NGS)用カスタム遺伝子パネルを構築し、その実行可能性について検討した。なお、本パネルは、1p/2q共欠失とIDH1/2遺伝子、TP53遺伝子、PTEN遺伝子、PDGFRA遺伝子、NF1遺伝子、RB1遺伝子、CDKN2A/B遺伝子およびCDK4遺伝子とTERT遺伝子のプロモーター領域(TERTp)変異を検出するために、神経膠腫診断に特化した遺伝子パネルである。当院で開発した中枢神経系腫瘍組織バンクから、神経膠腫患者106例(グレードII:19例、グレードIII:23例、グレードIV:64例)を選択し、本パネルを用いて解析した結果、乏突起膠腫で1p/19q共欠失が正確に検出され、グレードIV患者64例中56例にはIDH遺伝子が野生型の膠芽腫が同定され、うち33例にTERTp変異が認められた。また、PDGFRA遺伝子の変異と増幅は、TERTp遺伝子が野生型の膠芽腫では43%に、TERTp変異を有する膠芽腫では6%に認められ、分子遺伝情報に基づいた階層分類により、IDH遺伝子が野生型の膠芽腫では、明確に3グループに分類された。さらに、PDGFRA遺伝子変異、CDK4遺伝子およびPFGFRA遺伝子の増幅、CDKN2A/B遺伝子でのホモ接合性欠失やTERTp変異の欠如により特徴付けられた主要なクラスタが、高年齢、Ki-67高スコア、予後不良および脳室周囲腫瘍と有意に関連することが明らかにされた。以上の解析結果から、本パネルにより、PDGFRA遺伝子異常が高頻度に認められ、IDH遺伝子およびTERTp遺伝子変異が野生型を示す膠芽腫患者の各サブタイプが同定された。

Hirotsugu Noguchi, Natsumi Noguchi, Tetsuya Idichi, Yota Kawasaki, Mari Kirishima, Takashi Tasaki, Ikumi Kitazono, Michiko Horinouchi, Tsubasa Hiraki, Michiyo Higashi, Akihide Tanimoto . Case report of a lymphoepithelioma-like hepatocellular carcinoma with prominent lymphoplasmacytic infiltration . Human Pathology: Case Reports21 2020.9Reviewed

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier Inc.

Lymphoepithelioma-like carcinoma (LELC) of the liver is extremely rare, and lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is an uncommon variant form of HCC, exhibiting relatively good prognosis compared to conventional HCC. LELC is defined as a tumour composed of undifferentiated epithelial cells with densely infiltrating lymphoid stroma. LEL-HCC represents a unique immune response against tumour cells, which may contribute to the superior clinical outcomes. However, the exact aetiology remains unknown. We report a case of a 76-year-old man with a prior hepatitis B virus infection. A 20 mm tumour was detected in the liver. Microscopically, the tumour displayed characteristics of poorly differentiated HCC with a dense lymphocytic and plasma cell infiltration and was diagnosed as LEL-HCC. We describe a unique pathological finding with immunohistochemical data demonstrating T-cell dominant lymphocytic and polyclonal plasma cell infiltration, along with programmed death ligand 1 expression in the tumour cells and lymphocytes.

DOI： 10.1016/j.ehpc.2020.200402

Yoshiaki Shinden, Hazuki Saho, Yuki Nomoto, Ayako Nagata, Koji Minami, Akihiro Nakajo, Toshiaki Akahane, Tsubasa Hiraki, Akihide Tanimoto, Tetsuhiro Owaki, Yuko Kijima, Shoji Natsugoe . Breast cancer with an intraductal component that was proven genetically to be metastasis of contralateral breast cancer: a case report. . Surgical case reports6 ( 1 ) 215 - 215 2020.8Reviewed International journal

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

BACKGROUND: When diagnosing patients with bilateral breast cancer, it is challenging to determine the relationship between multiple breast cancer lesions at the individual patient level with certainty. CASE PRESENTATION: A 35-year-old Japanese woman was diagnosed with a left breast cancer. She was previously diagnosed with right pT3N3M0 stage IIIC breast cancer and underwent chemotherapy with targeted therapy, radiotherapy, and endocrine therapy as adjuvant treatment after mastectomy and axillary lymph node dissection. Approximately 2 years after the first surgery, her left breast cancer was preoperatively diagnosed as a contralateral primary breast cancer, and left mastectomy and axillary lymph node dissection were performed. Histopathologically, the tumor was determined to be invasive ductal carcinoma accompanied with several intraductal components. After a second surgery, mutation analysis of her bilateral breast cancer was performed in a clinical study, which revealed that her metachronous bilateral breast tumors had the same GATA3 and CSMD1 mutations. Thus, mutation analysis strongly supported her latter left breast cancer being a metastatic lesion from the former right breast cancer. Some difficulties in diagnosing bilateral breast cancer exist when determining whether they are double primary cancers or represent contralateral breast metastasis. The existence of intraductal components is a critical piece of information for suspecting primary lesions. However, this case demonstrated that metastatic contralateral breast lesions can have intraductal components. CONCLUSION: Herein we report a genetically proven contralateral breast metastasis with some intraductal components.

DOI： 10.1186/s40792-020-00966-y

Shinden Yoshiaki, Saho Hazuki, Nomoto Yuki, Nagata Ayako, Minami Koji, Nakajo Akihiro, Akahane Toshiaki, Hiraki Tsubasa, Tanimoto Akihide, Owaki Tetsuhiro, Kijima Yuko, Natsugoe Shoji . 対側乳房への転移が遺伝学的に明らかにされた乳管内成分を有する乳癌　1症例報告(Breast cancer with an intraductal component that was proven genetically to be metastasis of contralateral breast cancer: a case report) . Surgical Case Reports6 1 of 6 - 6 of 6 2020.8Reviewed

Language：English Publisher：Springer Berlin Heidelberg

症例は35歳女性で、左乳房に低エコー腫瘤を認めた。2年前に右乳癌と診断されて乳房切除術と腋窩リンパ節郭清を施行され、pT3N3M0ステージIIIC、Luminal HER2とされた。アジュバント療法として化学療法、放射線療法、内分泌療法を受け、トラスツズマブ投与終了の23ヵ月後、左乳房の上部外側に不規則な低エコー腫瘤が検出された。コア針生検にて病理学的に浸潤性乳管癌と診断し、CTと骨スキャンでは遠隔転移はみられなかった。術前診断ではT1N0M0ステージIAの対側原発性乳癌であり、左乳房切除術とセンチネルリンパ節生検を施行した。組織診の結果、浸潤性乳管癌であり、乳管内成分とリンパ浸潤がみられpT2N1M0とされた。乳管内成分を有することから左乳癌は原発性病変と考え、術後は化学療法と内分泌療法を行った。遺伝子解析を行ったところ、両側乳房に生じた異時性乳癌は同一のGATA3変異とCSMD1変異を有しており、左乳癌と右乳癌の転移であることを強く示唆する所見であった。この他に遺伝子変異は検出されず、ERBB2のコピー数は両病変とも同程度に増加していた。左乳房に対する術後12ヵ月、アジュバント療法を継続中であり、再発は認めていない。

Toshiaki Akahane, Ikumi Kitazono, Shintaro Yanazume, Masaki Kamio, Shinichi Togami, Ippei Sakamoto, Sachio Nohara, Seiya Yokoyama, Hiroaki Kobayashi, Tsubasa Hiraki, Shinsuke Suzuki, Shinichi Ueno, Akihide Tanimoto . Next-generation sequencing analysis of endometrial screening liquid-based cytology specimens: a comparative study to tissue specimens. . BMC medical genomics13 ( 1 ) 101 - 101 2020.7Reviewed International journal

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

BACKGROUND: Liquid-based cytology (LBC) is now a widely used method for cytologic screening and cancer diagnosis. Since the cells are fixed with alcohol-based fixatives, and the specimens are stored in a liquid condition, LBC specimens are suitable for genetic analyses. METHODS: Here, we established a small cancer gene panel, including 60 genes and 17 microsatellite markers for next-generation sequencing, and applied to residual LBC specimens obtained by endometrial cancer screening to compare with corresponding formalin-fixed paraffin-embedded (FFPE) tissues. RESULTS: A total of 49 FFPE and LBC specimens (n = 24) were analyzed, revealing characteristic mutations for endometrial cancer, including PTEN, CTNNB1, PIK3CA, and PIK3R1 mutations. Eight cases had higher scores for both tumor mutation burden (TMB) and microsatellite instability (MSI), which agree with defective mismatch repair (MMR) protein expression. Paired endometrial LBC, and biopsied and/or resected FFPE tissues from 7 cases, presented almost identical mutations, TMB, and MSI profiles in all cases. CONCLUSION: These findings demonstrate that our ad hoc cancer gene panel enabled the detection of therapeutically actionable gene mutations in endometrial LBC and FFPE specimens. Endometrial cancer LBC specimens offer an alternative and affordable source of molecular testing materials.

DOI： 10.1186/s12920-020-00753-6

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