Faculty Profiles - NAKAGURO Masato

Neuroendocrine cells associated with endocrine mucin-producing sweat gland carcinoma - a potential precursor lesion? Reviewed

Kawasaki T, Kubota T, Arai E, Ichihara S, Yata K, Nakaguro M, Kuroda M, Katoh R, Takahashi M, Horibe K, Naoe T, Hasebe T

VIRCHOWS ARCHIV Vol. 473 page： S182 2018.9

Low-grade intraductal carcinoma of the salivary gland with prominent oncocytic change: a newly described variant. Reviewed International journal

Nakaguro M, Urano M, Suzuki H, Yamada K, Sakaguchi A, Ogura K, Matsumoto T, Ono N, Asato T, Mikami Y, Imai H, Nagao T

Histopathology Vol. 73 ( 2 ) page： 314 - 320 2018.8

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

AIMS: Low-grade intraductal carcinoma (LG-IDC) is a clinically indolent malignant tumour of the salivary glands. Because of its rarity, the histological variants of LG-IDC have not been well characterised. Herein, we describe five LG-IDC cases with prominent oncocytic change in the major salivary glands. METHODS AND RESULTS: We examined five cases, three males and two females (mean age = 63 years), of LG-IDC with oncocytic change. The sites affected by LG-IDC were the parotid and submandibular glands. The lesions were macroscopically unilocular or multilocular cysts with a solid tumour arising from the cyst wall. Smaller tumour cell nests were also observed. As with classic LG-IDC, the cyst wall was surrounded by myoepithelial cells with no invasive component. The tumour cells had abundant oncocytic cytoplasm and proliferated in a low-papillary, tubular or cribriform pattern. Immunohistochemically, the tumour cells were diffusely positive for pan-cytokeratin, S100, mammaglobin and antimitochondria antibody, and were negative for androgen receptor and gross cystic disease fluid protein-15. Unlike classic LG-IDC, some of these cases demonstrated focal invagination of myoepithelial cells in the intraductal tumour. CONCLUSION: Oncocytic LG-IDC should be recognised as a histologically unique variant of LG-IDC. Awareness of this entity is important to avoid erroneous diagnosis and inappropriate treatment for histological mimics.

DOI： 10.1111/his.13517

β-catenin (CTNNB1) mutation and LEF1 expression in sinonasal glomangiopericytoma (sinonasal-type hemangiopericytoma) Reviewed

Yuka Suzuki, Shu Ichihara, Tomonori Kawasaki, Hiroyuki Yanai, Satoshi Kitagawa, Yoshie Shimoyama, Shigeo Nakamura, Masato Nakaguro

Virchows Archiv Vol. 473 ( 2 ) page： 235 - 239 2018.8

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

Sinonasal glomangiopericytoma (SN-GPC) is an uncommon mesenchymal tumor with myoid differentiation. Recently, mutations in exon 3 of the gene coding for β-catenin (CTNNB1) and its nuclear expression were discovered in SN-GPC. β-catenin protein is a key regulatory molecule of the canonical Wnt signaling pathway. The expression of β-catenin target proteins is not well characterized in SN-GPC. We examined three SN-GPCs by immunohistochemistry and CTNNB1 mutation analysis. All cases expressed nuclear β-catenin. We identified CTNNB1 exon 3 mutations in two analyzable cases. Lymphoid enhancer-binding factor 1 (LEF1), a protein downstream from β-catenin, was also expressed in all cases. Our results further characterized the activation of the Wnt signaling pathway caused by CTNNB1 exon 3 mutation and suggest the utility of LEF1 immunohistochemistry in the differential diagnosis of SN-GPC.

DOI： 10.1007/s00428-018-2370-9

Immunohistochemical assessment of the diagnostic utility of PD-L1: a preliminary analysis of anti-PD-L1 antibody (SP142) for lymphoproliferative diseases with tumour and non-malignant Hodgkin-Reed-Sternberg (HRS)-like cells. Reviewed International journal

Ayako Sakakibara, Kei Kohno, Ahmed E Eladl, Teerada Klaisuwan, Eri Ishikawa, Yuka Suzuki, Satoko Shimada, Masato Nakaguro, Yoshie Shimoyama, Taishi Takahara, Seiichi Kato, Naoko Asano, Shigeo Nakamura, Akira Satou

Histopathology Vol. 72 ( 7 ) page： 1156 - 1163 2018.6

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

AIMS: The programmed death 1 (PD1)/PD1 ligand (PD-L1) axis plays an important role in tumour cells escape from immune control. PD-L1 immunohistochemistry is a useful predictor of immunotherapy response, but is still not used widely in the diagnostic setting. Here we describe results using PD-L1 immunohistochemistry during routine diagnostics in lymphoma. METHODS AND RESULTS: Ninety-one lymphoproliferative disease cases sharing tumour and non-malignant Hodgkin-Reed-Sternberg (HRS)-like cells with and without Epstein-Barr virus (EBV) association were investigated by immunohistochemistry for PD-L1 (clone SP142). PD-L1 expression was present in more than 5% of tumour or non-malignant HRS-like cells in 100% of EBV+ classical (C) Hodgkin lymphoma (HL) (n = 10) and EBV-negative nodular sclerosis CHL (n = 8); 40% of EBV+ diffuse large B cell lymphoma, not otherwise specified (DLBCL-NOS) (n = 20); and 4% of nodal peripheral T cell lymphoma of follicular helper T cell type (PTCL-TFH) (n = 22). In contrast, nodular lymphocyte-predominant HL (n = 4), lymphocyte-rich CHL (n = 6), EBV+ hyperplasia (n = 8), plasmablastic lymphoma (n = 3) and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (n = 5) seldom exhibited PD-L1 in their large cells. Assessing PD-L1 positivity in tumour and non-malignant large cells was helpful in differentiating between CHL versus nodal PTCL-TFH (P < 0.0001) or EBV+ DLBCL-NOS (P = 0.0052) and between EBV+ DLBCL-NOS versus nodal PTCL-TFH (P = 0.0052), with PD-L1 expression indicating the first diagnosis in each of those sets. CONCLUSION: Immunohistochemical evaluation of PD-L1 expression in tumour and non-malignant HRS-like large cells may be useful for assessing either immune escape or immunodeficiency in their pathogenesis.

DOI： 10.1111/his.13475

Late-Onset Fulminant Myocarditis With Immune Checkpoint Inhibitor Nivolumab Reviewed

Shogo Yamaguchi, Ryota Morimoto, Takahiro Okumura, Yuta Yamashita, Tomoaki Haga, Tasuku Kuwayama, Tsuyoshi Yokoi, Hiroaki Hiraiwa, Toru Kondo, Yuki Sugiura, Naoki Watanabe, Naoaki Kano, Kei Kohno, Kenji Fukaya, Akinori Sawamura, Kenji Yokota, Hideki Ishii, Masato Nakaguro, Masashi Akiyama, Toyoaki Murohara

Canadian Journal of Cardiology Vol. 34 ( 6 ) page： 812.e1 - 812.e3 2018.6

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

A 60-year-old man was diagnosed with melanoma. After receiving 13 infusions of nivolumab, he had fulminant myocarditis. The myocardial biopsy specimen revealed extensive lymphocytic infiltration, interstitial edema, and myocardial necrosis, with predominant CD4+, CD8+, CD20− and programmed death-1− markers. Programmed death-1 ligand 1 (PD-L1) was predominantly expressed on the surface of the damaged myocardium. Although it is reported that myocarditis induced by the human anti-programmed death-1 inhibitor nivolumab therapy rarely occurred at &gt
2 months use in clinical trials, this case showed that even if at a late phase, long-term use of immune checkpoint inhibitors might to lead immune-related adverse events including myocarditis.

DOI： 10.1016/j.cjca.2018.03.007

Anaplastic variant of diffuse large B-cell lymphoma with hallmark cell appearance: Two cases highlighting a broad diversity in the diagnostics. Reviewed International journal

Ayako Sakakibara, Kei Kohno, Naoto Kuroda, Kenji Yorita, Nirmeen A Megahed, Ahmed E Eladl, Teerada Daroontum, Eri Ishikawa, Yuka Suzuki, Satoko Shimada, Masato Nakaguro, Yoshie Shimoyama, Akira Satou, Seiichi Kato, Yasushi Yatabe, Naoko Asano, Shigeo Nakamura

Pathology international Vol. 68 ( 4 ) page： 251 - 255 2018.4

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

The anaplastic variant of diffuse large B-cell lymphoma (A-DLBCL) is morphologically defined but remains an enigmatic disease in its clinicopathologic distinctiveness. Here, we report two cases involving Japanese women aged 59 years, both with A-DLBCL with the hallmark cell appearance and both indistinguishable from common and giant cell-rich patterns, respectively, of anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma. Case 1 was immunohistochemically positive for CD20, CD79a and OCT-2 but not for the other pan-B-cell markers, CD30 and ALK. Case 2 showed CD20 and CD30 positivity for 50% and 20% of tumor cells in addition to strong expression of p53 and MYC. Both were positive for fascin without Epstein-Barr virus association. Our cases provide additional support for the earlier reports that A-DLBCL exhibits clinicopathologic features distinct from ordinal diffuse large B-cell lymphoma (DLBCL), and documented its broader morphologic diversity than previously recognized. They also shed light on the unique feature of absent expression of pan-B-cell markers except for CD20 and CD79a, suggesting that A-DLBCL may biologically mimic a gray zone or intermediate lymphoma between DLBCL and classic Hodgkin lymphoma.

DOI： 10.1111/pin.12653

Promoter hypomethylation of SKI in autoimmune pancreatitis Reviewed

Yasuhiro Kinugawa, Takeshi Uehara, Kazuyuki Matsuda, Yukihiro Kobayashi, Tomoyuki Nakajima, Hideaki Hamano, Shigeyuki Kawa, Kayoko Higuchi, Noriko Hosaka, Satoshi Shiozawa, Hiroki Ishigame, Toshitsugu Nakamura, Yasuhiro Maruyama, Koh Nakazawa, Masato Nakaguro, Kenji Sano, Hiroyoshi Ota

Pathology Research and Practice Vol. 214 ( 4 ) page： 492 - 497 2018.4

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

The relationship between methylation abnormality and autoimmune pancreatitis (AIP)—a representative IgG4-related disease—has not yet been elucidated. We identified SKI might have a significant methylation abnormality in AIP through methylation array analysis using the Illumina Infinium Human Methylation 450K BeadChip array, and investigated the relationship of SKI with AIP clinicopathological features. The methylation rate of SKI was assessed by quantitative SYBR green methylation-specific PCR, and the degree of SKI expression in tissue specimens was assessed by immunohistochemistry in 10 AIP cases, 14 cases of obstructive pancreatitis area in pancreatic ductal adenocarcinoma (PDA) without a history of AIP, and 9 normal pancreas (NP) cases. The SKI methylation ratio was significantly lower in AIP than in PDA and NP. Additionally, the immunohistochemical staining-index (SI) score for SKI was significantly higher in AIP than NP, although there was no significant difference between AIP and PDA. There was a strong negative correlation between SI score and SKI methylation ratio, and between the serum concentrations of IgG4 and the SKI methylation ratio. There was a moderate positive correlation between the serum concentrations of IgG4 and SI. SKI is thought to be an oncogene indicating that SKI hypomethylation and carcinogenesis might be linked to AIP. Furthermore, the correlation between serum concentrations of IgG4 and SKI methylation levels suggest SKI might be involved in the pathogenesis of AIP. However, the role of SKI has not been clearly elucidated. Further studies are needed to understand further the function of SKI.

DOI： 10.1016/j.prp.2018.03.005

Beta-Catenin Expression and a CTNNB1 Mutation in Basal Cell Adenoma and Basal Cell Adenocarcinoma Reviewed

唾液腺腫瘍WHO分類2017・新規の組織型を理解する導管内癌の疾患概念と診断

中黒匡人, 長尾俊孝

日本病理学会会誌 Vol. 107 ( 1 ) page： 553 - 553 2018.4

Nakaguro Masato, Urano Makoto, Nagao Toshitaka

LABORATORY INVESTIGATION Vol. 98 page： 482 - 482 2018.3

Beta-Catenin Expression and a CTNNB1 Mutation in Basal Cell Adenoma and Basal Cell Adenocarcinoma Reviewed

Nakaguro Masato, Urano Makoto, Nagao Toshitaka

MODERN PATHOLOGY Vol. 31 page： 482 - 482 2018.3

基底細胞腺腫と基底細胞腺癌はbeta-cateninの発現とCTNNB1遺伝子の変異を伴う

中黒匡人, 浦野誠, 長尾俊孝

日本唾液腺学会誌 Vol. 58 page： 30 - 30 2017.11

In vivo histological diagnosis for gastric cancer using endocytoscopy Reviewed

Issei Tsurudome, Ryoji Miyahara, Kohei Funasaka, Kazuhiro Furukawa, Masanobu Matsushita, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Hiroki Kawashima, Osamu Watanabe, Masato Nakaguro, Akira Satou, Yoshiki Hirooka, Hidemi Goto

WORLD JOURNAL OF GASTROENTEROLOGY Vol. 23 ( 37 ) page： 6894 - 6901 2017.10

Language：English Publishing type：Research paper (scientific journal) Publisher：BAISHIDENG PUBLISHING GROUP INC

AIM
To examine usefulness of virtual biopsy using endocytoscopy by comparing the in vivo endocytoscopic and histopathological images of gastric cancers.
METHODS
Endocytoscopy was performed in 30 patients with early gastric cancer. Of these, 26 patients showed well differentiated adenocarcinomas, while 4 patients showed poorly differentiated adenocarcinomas (including one signet ring cell carcinoma). Cancerous and non-cancerous areas were observed after double staining with 0.05% crystal violet and 0.1% methylene blue. The endocytoscopic images obtained were evaluated by an expert endoscopist and an expert pathologist without knowledge of patient clinical data, and endocytoscopic and histopathological diagnoses were compared.
RESULTS
The endocytoscopic images of the cancerous area were assessed as evaluable in 25 (83.3%) and 27 (90%) patients by endoscopist A and pathologist B, respectively, and those of the non-cancerous area as evaluable in 28 (93.3%) and 23 (76.7%) patients by the endoscopist and pathologist, respectively. The sensitivity, specificity, and diagnostic accuracy of gastric cancer diagnosis using evaluable endocytoscopic images were 88.0% and 92.9%, and 90.6% by endoscopist A, and 88.9% and 91.3%, and 90.0% by pathologist B, respectively. Evaluation of the diagnostic concordance rate between the endoscopist and the pathologist by inter-observer agreement calculation revealed no significant difference between the two observers. The inter-observer agreement (kappa-value) for endocytoscopic diagnosis was 0.745.
CONCLUSION
Endocytoscopy is useful for the differentiation of cancerous from non-cancerous gastric mucosa, making it a promising tool for virtual biopsy.

DOI： 10.3748/wjg.v23.i37.6894

Clinicopathologic study on metachronous double cholangiocarcinomas of perihilar and subsequent distal bile duct origin Reviewed

Kentaro Shinohara, Yoshie Shimoyama, Tomoki Ebata, Yukihiro Yokoyama, Takashi Mizuno, Masato Nakaguro, Masato Nagino

SURGERY Vol. 162 ( 1 ) page： 84 - 93 2017.7

Language：English Publishing type：Research paper (scientific journal) Publisher：MOSBY-ELSEVIER

Background. Despite an increasing number of long-term survivors after the resection of perihilar cholangiocarcinoma, metachronous carcinoma in the remnant distal bile duct has not been well documented because of its rarity. The aim of this study was to clarify the feasibility of operative resection and the pathologic features for metachronous double cholangiocarcinomas.
Methods. Between 2003 and 2013, 6 patients underwent resections for both a primary perihilar cholangiocarcinoma and a metachronous distal cholangiocarcinoma. Their medical records were retrospectively reviewed.
Results. At a median of 42 months (range, 19-138 months) after the hepatectomy, a metachronous distal cholangiocarcinoma was detected by follow-up computed tomography and, interestingly, no symptoms were observed. Despite severe adhesions, a pancreatoduodenectomy was undertaken in all patients; there were no serious complications, and the procedure resulted in an R0 resection. Although 2 patients died of the disease after the second operation, the remaining 4 patients are now alive with (n = 1) or without recurrence. A pathologic survey showed that 4 patients had changes of biliary intraepithelial neoplasia-2/3 around their primary and metachronous lesions. The primary and metachronous cholangiocarcinomas showed histologic similarity in 4 of the 6 patients and immunohistochemical concordance in 3 of the 6 patients.
Conclusion. Pancreatoduodenectomy for metachronous distal cholangiocarcinoma can lead to a favorable prognosis. Careful observation after the resection of perihilar cholangiocarcinoma is,mandatory to detect this potentially curable disease. Pathologically, some of the multicentric cholangiocarcinomas present histologic and immunohistochemical similarities.

DOI： 10.1016/j.surg.2016.12.034