Faculty Profiles - NAKAGURO Masato

Calculating the Tumor Nuclei Content for Comprehensive Cancer Panel Testing. Reviewed International journal

Masashi Mikubo, Katsutoshi Seto, Atsuko Kitamura, Masato Nakaguro, Yukinori Hattori, Nagako Maeda, Tatsuhiko Miyazaki, Kazuko Watanabe, Hideki Murakami, Tetsuya Tsukamoto, Tetsuya Yamada, Shiro Fujita, Katsuhiro Masago, Shakti Ramkissoon, Jeffrey S Ross, Julia Elvin, Yasushi Yatabe

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer Vol. 15 ( 1 ) page： 130 - 137 2020.1

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

Comprehensive genetic panel testing generally requires that the analyzed tissues have a percent tumor nuclei (%TN) content of 20% or more to achieve assay performance comparable to the validated specifications. Pathologists play a crucial role in ensuring that the optimal results are achieved by accurately assigning %TN content of the available specimens and selecting the best material to submit for sequencing. This study addresses the issues in evaluating %TN, such as intraobserver variability, and examines whether focused training and feedback can improve pathologist performance. Nine referring institution pathologists (all board-certified and working at the core institute and the alignment hospitals under the National Cancer Genome scheme) evaluated 18 tumors that had been subjected to comprehensive genetic panel testing with the FoundationOne CDx assay. The %TN estimates provided by referring institution pathologists were compared with two standards: %TN assigned by the tumor sequencing institution's pathologist (a board-certified pathologist at Foundation Medicine, Inc.) and the computational %TN estimated from the mutant allele frequencies after sequencing was completed. The pathologists generally overestimated %TN in the first pretraining round of the evaluation, and the differences in the averaged %TN from the tumor sequencing institution and computational standards were statistically significant. However, the posttraining second-round results became significantly concordant with the standards. This study suggests that %TN content is empirically overestimated but the evaluation skill can be improved by providing a training and feedback program.

DOI： 10.1016/j.jtho.2019.09.081

Multi-scale Domain-adversarial Multiple-instance CNN for Cancer Subtype Classification with Unannotated Histopathological Images Reviewed

Color information from linked color imaging is associated with invasion depth and vascular diameter in superficial esophageal squamous cell carcinoma. Reviewed International journal

Kenichi Kobayashi, Ryoji Miyahara, Kohei Funasaka, Kazuhiro Furukawa, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Hiroki Kawashima, Masato Nakaguro, Yuki Okumura, Yoshiki Hirooka, Mitsuhiro Fujishiro

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society Vol. 32 ( 1 ) page： 65 - 73 2020.1

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

OBJECTIVES: Accurate diagnosis of invasion depth is important for reliable treatment of esophageal squamous cell carcinoma (ESCC), but it is limited to the muscularis mucosae to slight submucosal invasion (MM/SM1). The diagnostic accuracy of invasion depth is unsatisfactory and remains to be improved. We aimed to investigate the association between the color of the superficial ESCC and invasion depth using linked color imaging (LCI) under light-emitting diode (LED) light sources. METHODS: Lesions diagnosed as superficial ESCC were observed using white light imaging and then by LCI. The color values were calculated using Commission Internationale de l'Eclariage - L*a*b* color space, and the color difference was calculated according to invasion depth. The vascular diameters and vascular angles of the intrapapillary capillary loops were pathologically analyzed. Their correlation with mucosal color was also investigated by LCI. RESULTS: In all, 52 lesions from 48 patients were analyzed. On the basis of invasion depth, the color difference between the normal mucosa and the lesion was larger in the MM/SM1 or deeper group than in the epithelium and the lamina propria mucosa (EP/LPM) group using LCI (P = 0.025). The vascular diameter was positively correlated with the b* color value (correlation coefficient = 0.302, P = 0.033). CONCLUSION: Observation using LCI under LED light sources may improve the endoscopic diagnosis of the invasion depth of superficial ESCC. Further research is needed to validate its usefulness. (UMIN000024615).

DOI： 10.1111/den.13469

中黒匡人, 長尾俊孝

病理と臨床 Vol. 38 ( 1 ) page： 79 - 83 2020.1

Noriaki Hashimoto, Daisuke Fukushima, Ryoichi Koga, Yusuke Takagi, Kaho Ko, Kei Kohno, Masato Nakaguro, Shigeo Nakamura, Hidekata Hontani, Ichiro Takeuchi

2020 IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR) page： 3851 - 3860 2020

Genetic Diagnosis Based on a Comprehensive Fusion Gene Analysis of Pediatric Malignant Solid Tumors Reviewed

Daisuke Ichikawa, Hideki Muramatsu, Yusuke Okuno, Motoharu Hamada, Rieko Taniguchi, Eri Nishikawa, Nozomu Kawashima, Atsushi Narita, Nobuhiro Nishio, Yoshie Shimoyama, Masato Nakaguro, Shigeo Nakamura, Seiji Kojima, Atsuko Nakazawa, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 66 page： S61 - S61 2019.12

唾液腺導管癌における脂質関連蛋白発現の臨床病理学的意義 Reviewed

平井秀明, 多田雄一郎, 中黒匡人, 川北大介, 佐藤由紀子, 志村智隆, 塚原清彰, 加納里志, 小澤宏之, 大上研二, 佐藤雄一郎, 伏見千宙, 清水顕, 高瀬総一郎, 岡田拓朗, 佐藤宏樹, 今西順久, 大塚邦憲, 渡部佳弘, 酒井昭博, 戎本浩史, 富樫孝文, 植木雄志, 太田久幸, 三枝奈津季, 高橋秀聡, 安藤瑞生, 浦野誠, 花澤豊行, 長尾俊孝

日本唾液腺学会誌 Vol. 60 page： 24 - 25 2019.11

がんパネルシーケンスにおける病理所見と遺伝子変異頻度から判定した腫瘍細胞核含有量の比較 Reviewed

真砂勝泰, 瀬戸克年, 北村淳子, 中黒匡人, 服部行紀, 前田永子, 宮崎龍彦, 渡邊和子, 村上秀樹, 塚本徹哉, 山田鉄也, 藤田史郎, 谷田部恭

肺癌 Vol. 59 ( 6 ) page： 918 - 918 2019.11

BK virus-associated viruria and viremia in a patient with lymphangioleiomyomatosis after lung re-transplantation: A case report and review of the literature on BK virus infection post-lung transplantation. Reviewed International journal

Junya Okumura, Yoshio Nakahara, Masato Nakaguro, Yuichiro Shindo, Tetsunari Hase, Keiko Wakahara, Naozumi Hashimoto, Yoshinori Hasegawa

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy Vol. 25 ( 10 ) page： 820 - 824 2019.10

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

The BK virus (BKV) is a member of the polyomaviridae family of DNA viruses. BKV reactivates under a highly immunosuppressed state and causes renal dysfunction. In renal transplant patients, BKV infection leads to tubular impairment and loss of transplanted kidney grafts. However, few studies have reported on the relationship between BKV and lung transplantation. Adjustment of the dosage of immunosuppressants is needed in some cases, but the treatment method has not been established. Here, we report a case of BKV-associated viruria and viremia in a patient with lymphangioleiomyomatosis (LAM) after lung re-transplantation. A 44-year-old female refractory LAM patient who had undergone lung re-transplantation 3 months earlier was diagnosed with BKV-associated viruria and viremia. Urine cytology indicated decoy cells and the urine and serum polymerase chain reaction test was positive for BKV. As scheduled after re-transplantation surgery, immunosuppressive drugs were progressively reduced. This patient was considered to have experienced spontaneous BKV-associated viremia and viruria. Review of the literature suggested that 17%-42% of BKV-associated viruria cases have been reported after lung transplantation, but cases of BKV-associated nephropathy are rarely reported. Based on the present case, doctors involved in lung transplantation should monitor patients for BKV infection. Decoy cell monitoring by urine cytology is a useful screening method in the follow-up observation after lung transplantation. Early-stage interventions may prevent BKV-associated nephropathy even in patients who have developed BKV viremia, and sirolimus can be administered to patients with histories of BKV infection if they are carefully monitored.

DOI： 10.1016/j.jiac.2019.04.002

ちょっと気になる胆・膵画像ティーチングファイルから(第43回) 術前診断が困難であった膵lymphangiomaの1例 Reviewed

小川浩, 竹原康雄, 長縄慎二, 高見秀樹, 中黒匡人

胆と膵 Vol. 40 ( 10 ) page： 841 - 844 2019.10

Fatal case of TAFRO syndrome associated with over-immunosuppression: a case report and review of the literature. Reviewed

Takaharu Matsuhisa, Noriyuki Takahashi, Masato Nakaguro, Motoki Sato, Eri Inoue, Shiho Teshigawara, Yukihiro Ozawa, Takeshi Kondo, Shigeo Nakamura, Juichi Sato, Nobutaro Ban

Nagoya journal of medical science Vol. 81 ( 3 ) page： 519 - 528 2019.8

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

TAFRO syndrome is a novel disease concept characterized by Thrombocytopenia, Anasarca, myeloFibrosis, Renal dysfunction, Organomegaly, multiple lymphadenopathy and a histopathological pattern of atypical Castleman's disease. A 58-year-old man was diagnosed as TAFRO syndrome by clinical and histopathological findings. After receiving intensive immunosuppressive therapy, his thrombocytopenia and anasarca had not improved. He developed complications such as methicillin-resistant Staphylococcus aureus sepsis, gastrointestinal bleeding, peritonitis caused by Stenotrophomonas maltophilia, gastrointestinal perforation, and disseminated candidiasis resulting in death. Autopsy revealed disseminated candidiasis and hemophagocytic lymphohistiocytosis, with no evidence of TAFRO syndrome. During treatment, we regarded his lasting thrombocytopenia and anasarca as insufficient control of TAFRO syndrome. However, the autopsy revealed that thrombocytopenia was caused by secondary hemophagocytic lymphohistiocytosis caused by over-immunosuppression. We reviewed the published literature to identify indicators of adequate treatment, which suggested improvement of platelet count and anasarca several weeks after initial therapy. This indicated that we could not depend on the platelet count and anasarca in acute medical care after initial treatment. We should treat TAFRO syndrome based on patients' clinical status and obviate the risk of treatment-related complications caused by over-immunosuppression.

DOI： 10.18999/nagjms.81.3.519

Diagnostic Significance of HRAS Mutations in Epithelial-Myoepithelial Carcinomas Exhibiting a Broad Histopathologic Spectrum. Reviewed International journal

Makoto Urano, Masato Nakaguro, Yoshinari Yamamoto, Hideaki Hirai, Maki Tanigawa, Natsuki Saigusa, Akira Shimizu, Kiyoaki Tsukahara, Yuichiro Tada, Kouhei Sakurai, Madoka Isomura, Yuki Okumura, Hiroshi Yamaguchi, Jun Matsubayashi, Toshitaka Nagao

The American journal of surgical pathology Vol. 43 ( 7 ) page： 984 - 994 2019.7

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

Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland tumor that is histologically characterized by biphasic tubular structures composed of inner ductal and outer clear myoepithelial cells. Because of its histologic variety, it is sometimes challenging to make an accurate diagnosis, and useful ancillary tests are essential for this purpose. We investigated 87 cases of EMC arising in the major and minor salivary glands and seromucinous glands in the nasal cavity or bronchus to describe the histologic features and mutation status of selected key oncogenes. Classic EMC accounted for 40.2% of all cases. Other cases showed various growth patterns and cytologic features in addition to the typical histology; cribriform patterns, a basaloid appearance, and sebaceous differentiation were relatively common (17.2% to 18.4%), whereas oncocytic/apocrine, papillary-cystic, double-clear, squamous, psammomatous, Verocay-like, and high-grade transformation were rare. HRAS mutations were found in 82.7% of EMCs and were concentrated in codon 61. There was no significant correlation between the HRAS mutation status and the histology. No EMC ex pleomorphic adenoma cases had HRAS mutations. PIK3CA and/or AKT1 mutations were the second most frequent mutations (20.7%, 6.5%, respectively) and almost always cooccurred with HRAS mutations. It is noteworthy that the HRAS mutation was not identified in any salivary gland tumor entities manifesting EMC-like features, including adenoid cystic carcinoma, pleomorphic adenoma, basal cell adenoma/adenocarcinoma, and myoepithelial carcinoma. We conclude that HRAS mutations are a frequent tumorigenic gene alteration in EMC, despite its histologic diversity. This study provides further insight into strategies for diagnosing EMC and discriminating it from its mimics.

DOI： 10.1097/PAS.0000000000001258

A case of human pancreatic eurytremiasis Reviewed

Ogawa Hiroshi, Takehara Yasuo, Naganawa Shinji, Yamaguchi Junpei, Nakaguro Masato

ABDOMINAL RADIOLOGY Vol. 44 ( 4 ) page： 1213-1216 2019.4

Acrodermatitis continua of Hallopeau with dense infiltration of IgG<sub>4</sub> -positive cells in the lesional dermis. Reviewed International journal

Ogawa-Momohara M, Muro Y, Nakaguro M, Takeichi T, Kono M, Akiyama M

The British journal of dermatology Vol. 180 ( 4 ) page： 941 - 942 2019.4

Utility of linked color imaging for endoscopic diagnosis of early gastric cancer. Reviewed International journal

Toshihisa Fujiyoshi, Ryoji Miyahara, Kohei Funasaka, Kazuhiro Furukawa, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Hiroki Kawashima, Masato Nakaguro, Masahiro Nakatochi, Yoshiki Hirooka

World journal of gastroenterology Vol. 25 ( 10 ) page： 1248 - 1258 2019.3

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

BACKGROUND: Linked color imaging (LCI) is a method of endoscopic imaging that emphasizes slight differences in red mucosal color. AIM: To evaluate LCI in diagnostic endoscopy of early gastric cancer and to compare LCI and pathological findings. METHODS: Endoscopic images were obtained for 39 patients (43 lesions) with early gastric cancer. Three endoscopists evaluated lesion recognition with white light imaging (WLI) and LCI. Color values in Commission Internationale de l'Eclairage (CIE) 1976 L*a*b* color space were used to calculate the color difference (ΔE) between cancer lesions and non-cancer areas. After endoscopic submucosal dissection, blood vessel density in the surface layer of the gastric epithelium was evaluated pathologically. The identical region of interest was selected for analyses of endoscopic images (WLI and LCI) and pathological analyses. RESULTS: LCI was superior for lesion recognition (P < 0.0001), and ΔE between cancer and non-cancer areas was significantly greater with LCI than WLI (29.4 vs 18.6, P < 0.0001). Blood vessel density was significantly higher in cancer lesions (5.96% vs 4.15%, P = 0.0004). An a* cut-off of ≥ 24 in CIE 1976 L*a*b* color space identified a cancer lesion using LCI with sensitivity of 76.7%, specificity of 93.0%, and accuracy of 84.9%. CONCLUSION: LCI is more effective for recognition of early gastric cancer compared to WLI as a result of improved visualization of changes in redness. Surface blood vessel density was significantly higher in cancer lesions, and this result is consistent with LCI image analysis.

DOI： 10.3748/wjg.v25.i10.1248