Faculty Profiles - YAMAMOTO HIDETAKA

Papers - YAMAMOTO HIDETAKA

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PD-L1 and IDO-1 expression in undifferentiated pleomorphic sarcoma: The associations with tumor infiltrating lymphocytes, dMMR and HLA class I

Shin Ishihara, Yuichi Yamada, Takeshi Iwasaki, Masato Yoshimoto, Yu Toda, Kenichi Kohashi, Hidetaka Yamamoto, Yoshihiro Matsumoto, Yasuharu Nakashima, Yoshinao Oda

Oncology Reports 45 ( 1 ) 379 - 389 2021.1

Publishing type：Research paper (scientific journal)

© 2021 Spandidos Publications. All rights reserved. The prognosis of undifferentiated pleomorphic sarcoma (UPS) is generally unfavorable. Recently, clinical trials such as SARC028 demonstrated the utility of cancer immunotherapy for soft tissue sarcomas. The aim of the present study was to assess the expression of PD-L1 and IDO-1 as prognostic factors and therapeutic targets. A total of 52 primary UPS cases were retrieved and two UPS cell lines were utilized for supplementary analysis. Immunohistochemical staining of anti-PD-L1 (28-8), IDO-1, CD8, CD4, CD3, HLA class I, MSH2, MSH6, MLH1 and PMS2 was carried out. Immunohistochemically, 19 of 52 (36.5%) cases showed PD-L1 expression at least focally (≥1%) and 5 of 52 (9.62%) showed strong PD-L1 expression (≥50%). Overall, 25 of 52 (48.1%) cases expressed IDO-1 (≥1%). Two tumors were evaluated as having deficient mismatch repair and six tumors as having the loss of HLA class I. PD-L1 expression (≥1%) was significantly related to the infiltration of CD8- and CD3-positive lympho- cytes, but strong PD-L1 expression (≥50%) did not present a significant relationship with tumor-infiltrating lymphocytes. IDO-1 expression was also associated with CD8-, CD4-, and CD3-positive lymphocytes. In vitro, both PD-L1 and IDO-1 were induced by IFN-γ stimulation. In survival analysis, strong PD-L1 expression (≥50%) was a significant poor prognostic factor, while IDO-1 expression (≥1%) was a favorable one. In conclusion, UPS was shown to frequently express PD-L1 and IDO-1. It was suggested that PD-L1 expression (≥50%) and IDO-1 expression are poor and favorable prognostic factors of UPS patients, respectively.

DOI： 10.3892/or.2020.7837

Genomic Sequencing of Cancer-related Genes in Sinonasal Squamous Cell Carcinoma and Coexisting Inverted Papilloma. International journal

Ryutaro Uchi, Rina Jiromaru, Ryuji Yasumatsu, Hidetaka Yamamoto, Takahiro Hongo, Tomomi Manako, Kuniaki Sato, Kazuki Hashimoto, Takahiro Wakasaki, Mioko Matsuo, Takashi Nakagawa

Anticancer research 41 ( 1 ) 71 - 79 2021.1

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

BACKGROUND: The genetic basis of sinonasal inverted papilloma (SNIP)-derived squamous cell carcinoma (SCC) has not yet been well characterized. AIM: To characterize the genetic abnormalities of SNIP and SNIP-derived SCC and to uncover their differences. MATERIALS AND METHODS: Mutations of 409 genes were analyzed using amplicon targeted sequencing in a total of six papilloma/carcinoma samples from four patients with SNIP-derived SCC. RESULTS: The genes that were mutated in multiple cases were epidermal growth factor receptor (EGFR) (3/6), cyclin-dependent kinase inhibitor 2A (CDKN2A) (3/6), lysine methyltransferase 2D (KMT2D) (3/6), tumor protein p53 (TP53) (3/6), neurofibromin 1 (NF1) (3/6), phosphodiesterase 4D interacting protein (PDE4DIP) (3/6), cytochrome P450 family 2 subfamily D member 6 (CYP2D6) (2/6), fms-related receptor tyrosine kinase 4 (FLT4) (2/6) and myosin heavy chain 9 (MYH9) (2/6). Of the two cases analyzed in the papilloma-oncology carcinoma pair, one did not have any common mutations; the other showed a staged functional deletion of TP53 during the process of malignant transformation from SNIP to SCC. CONCLUSION: CDKN2A, KMT2D, NF1, PDE4DIP, CYP2D6, FLT4, and MYH9 were identified as candidate novel SNIP-derived SCC-related genes.

DOI： 10.21873/anticanres.14752

Breast metastasis from pelvic high-grade serous adenocarcinoma: a report of two cases. International journal

Yurina Harada, Makoto Kubo, Masaya Kai, Mai Yamada, Karen Zaguirre, Tatsuhiro Ohgami, Hideaki Yahata, Yoshihiro Ohishi, Hidetaka Yamamoto, Yoshinao Oda, Masafumi Nakamura

Surgical case reports 6 ( 1 ) 317 - 317 2020.12

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

BACKGROUND: Metastatic tumors to the breast reportedly account for 0.5% to 2.0% of all malignant breast diseases. Such metastatic tumors must be differentiated from primary breast cancer. Additionally, few reports have described metastases of gynecological cancers to the breast. We herein report two cases of metastasis of pelvic high-grade serous adenocarcinoma to the breast. CASE PRESENTATION: The first patient was a 57-year-old woman with a transverse colon obstruction. Colostomy was performed, but the cause of the obstruction was unknown. We found scattered white nodules disseminated throughout the abdominal cavity and intestinal surface. Follow-up contrast-enhanced computed tomography (CT) showed an enhanced nodule outside the right mammary gland. Core needle biopsy (CNB) of the right breast mass was conducted, and immunohistochemical staining of the mass suggested a high-grade serous carcinoma of female genital tract origin. We diagnosed the patient's condition as breast and lymph node metastasis of a high-grade serous carcinoma of the female genital tract. After chemotherapy for stage IVB peritoneal cancer, tumor reduction surgery was performed. The second patient was a 71-year-old woman with a medical history of low anterior resection for rectal cancer at age 49, partial right thyroidectomy for follicular thyroid cancer at age 53, and left lower lung metastasis at age 57. Periodic follow-up CT showed peritoneal dissemination, cancerous peritonitis, and pericardial effusion, and the patient was considered to have a cancer of unknown primary origin. Contrast-enhanced CT showed an enhanced nodule in the left mammary gland with many enhanced nodules and peritoneal thickening in the abdominal cavity. CNB of the left breast mass was conducted, and immunohistochemical staining of the mass suggested a high-grade serous carcinoma of female genital tract origin. After chemotherapy for stage IVB peritoneal cancer, tumor reduction surgery was performed. CONCLUSIONS: We experienced two rare cases of intramammary metastasis of high-grade serous carcinoma of female genital tract origin. CNB was useful for confirming the histological diagnosis of these cancers that had originated from other organs. A correct diagnosis of such breast tumors is important to ensure quick and appropriate treatment.

DOI： 10.1186/s40792-020-01090-7

Characterization of parotid gland tumors: added value of permeability MR imaging to DWI and DCE-MRI Reviewed International journal

Hidetake Yabuuchi, Takeshi Kamitani, Koji Sagiyama, Yuzo Yamasaki, Tomoyuki Hida, Yuko Matsuura, Takuya Hino, Yuriko Murayama, Ryuji Yasumatsu, Hidetaka Yamamoto

European Radiology 30 ( 12 ) 6402 - 6412 2020.12

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

© 2020, European Society of Radiology. Objectives: To determine added value of permeability MRI in parotid tumor characterization to T2-weighted imaging (T2WI), semi-quantitative analysis of time-intensity curve (TIC), and intra-voxel incoherent motion diffusion-weighted imaging (IVIM-DWI). Methods: This retrospective study was approved by the institutional review board, and the informed consent was waived. Sixty-one parotid tumors in 61 patients were examined using T2WI, IVIM-DWI, and permeability MRI. TIC patterns were categorized as persistent, washout, or plateau. Signal intensity ratio of lesion-to-muscle on T2WI, apparent diffusion coefficients (ADCs), D and f values from IVIM-DWI, and Ktrans, kep, Ve, and Vp values from permeability MRI were measured. Multiple comparisons were applied to determine whether any differences among 4 histopathologic types (pleomorphic adenomas, Warthin’s tumors, other benign tumors, and malignant tumors) existed. Diagnostic accuracy was compared before and after modification diagnosis referring to permeability MRI. In a validation study, 60 parotid tumors in 60 patients were examined. Results: ADC and D values of malignant tumors were significantly lower than those of benign tumors other than Warthin’s tumors, but higher than those of Warthin’s tumors. kep and Vp values of Warthin’s tumors were significantly higher than those of malignant tumors. Multivariate analyses showed that TIC pattern, D, and kep values were suitable parameters. McNemar’s test showed a significant increase of sensitivity (11/12, 92%) and specificity (46/49, 94%) with adding kep. The validation study yielded high sensitivity (14/16, 88%) and specificity (41/44, 93%). Conclusion: Permeability MRI offers added value to IVIM-MRI and semi-quantitative TIC analysis of DCE-MRI in characterization of parotid tumors Key Points: • Permeability MR imaging offers added value in the characterization of parotid gland tumors in combination with semi-quantitative TIC analysis and IVIM analyses with D parameter. • The combination of TIC pattern, D, and kepmight facilitate accurate characterization of parotid gland tumor, thereby avoiding unnecessary surgery for benign tumors or delayed treatment for malignant tumors. • A combination of permeability and diffusion MR imaging can be used to guide the selection of an appropriate biopsy site.

DOI： 10.1007/s00330-020-07004-3

Clinicopathological features and immunohistochemical utility of NTRK-, ALK-, and ROS1-rearranged papillary thyroid carcinomas and anaplastic thyroid carcinomas Reviewed International journal

Yui Nozaki, Hidetaka Yamamoto, Takeshi Iwasaki, Masanobu Sato, Rina Jiromaru, Takahiro Hongo, Ryuji Yasumatsu, Yoshinao Oda

Human Pathology 106 82 - 92 2020.12

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

© 2020 NTRK1/3, ALK, and ROS1 translocations have been reported in a minor subset of papillary thyroid carcinomas (PTCs). We aimed to elucidate the prevalence and clinicopathological characteristics of these gene rearrangements and the utility of immunohistochemistry (IHC) in PTC and anaplastic thyroid carcinoma (ATC). We screened nonradiation-exposed cases of 307 PTCs and 16 ATCs by IHC for pan-Trk, ALK, and ROS1, followed by fluorescence in situ hybridization (FISH). In the PTC group, IHC for pan-Trk, ALK, and ROS1 was positive in 18 cases (5.9%), 1 case (0.3%), and 12 cases (3.9%), respectively. Among the pan-Trk IHC–positive cases (n = 18), 2 cases (11.1%; 0.7% of all PTCs) had NTRK1 or NTRK3 gene rearrangement with conventional PTC histology. The ALK IHC–positive case (n = 1) was the follicular variant of PTC with consistent ALK gene rearrangement. ROS1 gene rearrangement was not detectable in the ROS1 IHC–positive PTCs (0/12) by FISH. Most (approximately 70%) of the pan-Trk or ROS1 IHC–positive/FISH–negative cases had BRAF gene mutation with conventional PTC morphology. In the ATC group, neither ALK nor ROS1 IHC was positive, whereas pan-Trk IHC was positive in 1 case (6.3%) in which NTRK1 gene rearrangement was confirmed by FISH. These results suggest that NTRK, ALK, and ROS1 rearrangements are rare molecular events in nonradiation-exposed Japanese patients with PTC and ATC. Although IHC is not an entirely specific surrogate for these abnormalities and does not serve as a stand-alone companion diagnosis, the combined use of IHC and molecular testing may be helpful for determining promising therapeutic strategies with tyrosine kinase inhibitors.

DOI： 10.1016/j.humpath.2020.09.004

Chronic inflammatory changes and oxidative stress in the background of “pancreatic ductal adenocarcinoma concomitant with intraductal papillary mucinous neoplasm” Reviewed International journal

Ryota Matsuda, Yoshihiro Miyasaka, Yuichi Yamada, Jun Kawata, Kukiko Sakihama, Takeo Yamamoto, Kiyoshi Saeki, Hidetaka Yamamoto, Yoshihiro Ohishi, Yutaka Koga, Masafumi Nakamura, Yoshinao Oda

Virchows Archiv 477 ( 6 ) 799 - 806 2020.12

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

© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Cases of “pancreatic ductal adenocarcinoma (PDAC) concomitant with intraductal papillary mucinous neoplasm” (IPMN) have multiple PDAC lesions more frequently than cases of “PDAC without IPMN”. However, the mechanism of carcinogenesis in this former disease category remains unknown. The main objective of this work was thus to investigate the effects of chronic inflammation on carcinogenesis in PDAC cases. We selected 31 “PDAC concomitant with IPMN” patients and 58 “PDAC without IPMN” patients and pathologically evaluated their background pancreatic parenchyma. Fibrosis and inflammation scores of background pancreas were higher in “PDAC concomitant with IPMN” than in “PDAC without IPMN” (P < 0.0001 and P < 0.0001, respectively), whereas the fatty infiltration score of background pancreas was high in “PDAC without IPMN” (P = 0.0024). Immunohistochemically, the expression of 8-hydroxy-2′-deoxyguanosine (8-OHDG), an oxidative stress marker, in the background pancreas was high in “PDAC concomitant with IPMN” compared with that in “PDAC without IPMN” (P < 0.0001). Chronic inflammation activates oxidative stress in tissue throughout the pancreas and probably confers susceptibility to tumorigenesis in “PDAC concomitant with IPMN”.

DOI： 10.1007/s00428-020-02844-2

Efficacy of endoscopic ultrasound with artificial intelligence for the diagnosis of gastrointestinal stromal tumors Reviewed

Yosuke Minoda, Eikichi Ihara, Keishi Komori, Haruei Ogino, Yoshihiro Otsuka, Takatoshi Chinen, Yasuo Tsuda, Koji Ando, Hidetaka Yamamoto, Yoshihiro Ogawa

Journal of Gastroenterology 55 ( 12 ) 1119 - 1126 2020.12

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

© 2020, Japanese Society of Gastroenterology. Background: Although endoscopic ultrasound (EUS) is reported to be suitable for determining the layer from which subepithelial lesions (SELs) originate, it is difficult to distinguish gastrointestinal stromal tumor (GIST) from non-GIST using only EUS images. If artificial intelligence (AI) can be used for the diagnosis of SELs, it should provide several benefits, including objectivity, simplicity, and quickness. In this pilot study, we propose an AI diagnostic system for SELs and evaluate its efficacy. Methods: Thirty sets each of EUS images with SELs ≥ 20 mm or < 20 mm were prepared for diagnosis by an EUS diagnostic system with AI (EUS-AI) and three EUS experts. The EUS-AI and EUS experts diagnosed the SELs using solely the EUS images. The concordance rates of the EUS-AI and EUS experts’ diagnoses were compared with the pathological findings of the SELs. Results: The accuracy, sensitivity, and specificity for SELs < 20 mm were 86.3, 86.3, and 62.5%, respectively for the EUS-AI, and 73.3, 68.2, and 87.5%, respectively, for the EUS experts. In contrast, accuracy, sensitivity, and specificity for SELs ≥ 20 mm were 90.0, 91.7, and 83.3%, respectively, for the EUS-AI, and 53.3, 50.0, and 83.3%, respectively, for the EUS experts. The area under the curve for the diagnostic yield of the EUS-AI for SELs ≥ 20 mm (0.965) was significantly higher than that (0.684) of the EUS experts (P = 0.007). Conclusion: EUS-AI had a good diagnostic yield for SELs ≥ 20 mm. EUS-AI has potential as a good option for the diagnosis of SELs.

DOI： 10.1007/s00535-020-01725-4

Prognostic impact of CRTC1/3-MAML2 fusions in salivary gland mucoepidermoid carcinoma: A multiinstitutional retrospective study Reviewed International journal

Yoshihide Okumura, Satsuki Nakano, Takayuki Murase, Kaori Ueda, Daisuke Kawakita, Toshitaka Nagao, Kimihide Kusafuka, Makoto Urano, Hidetaka Yamamoto, Satoshi Kano, Kiyoaki Tsukahara, Kenji Okami, Toru Nagao, Nobuhiro Hanai, Hiroshi Iwai, Ryo Kawata, Yuichiro Tada, Ken Ichi Nibu, Hiroshi Inagaki

Cancer Science 111 ( 11 ) 4195 - 4204 2020.11

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

© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association Mucoepidermoid carcinoma (MEC) is rare, but the most common primary malignancy of the salivary gland and not infrequent in young individuals. CRTC1/3-MAML2 fusions are frequently detected in MEC and are useful as a diagnostic biomarker. However, there has been debate as to whether the fusions have prognostic significance. In this study, we retrospectively collected 153 salivary gland MEC cases from 11 tertiary hospitals in Japan. As inclusion criteria, the MEC patients in this study had curative surgery as the initial treatment, received no preoperative treatment, and had no distant metastasis at the time of the initial surgery. The MEC diagnosis was validated by a central pathology review by five expert salivary gland pathologists. The CRTC1/3-MAML2 fusions were detected using FISH and RT-PCR. In 153 MEC cases, 90 (58.8%) were positive for CRTC1/3-MAML2 fusions. During the follow-up period, 28 (18.3%) patients showed tumor recurrence and 12 (7.8%) patients died. The presence of the fusions was associated with favorable tumor features. Of note, none of the fusion-positive patients died during the follow-up period. Statistical analysis showed that the presence of the fusions was a prognostic indicator of a better overall survival in the total and advanced-stage MEC cohorts, but not in the early-stage MEC cohort. In conclusion, CRTC1/3-MAML2 fusions are an excellent biomarker for favorable overall survival of patients with salivary gland MEC.

DOI： 10.1111/cas.14632

Frequent MN1 gene mutations in malignant peripheral nerve sheath tumor

Izumi Kinoshita, Yuichi Yamada, Kenichi Kohashi, Hidetaka Yamamoto, Takeshi Iwasaki, Shin Ishihara, Yu Toda, Yoshihiro Ito, Yousuke Susuki, Kengo Kawaguchi, Toshio Ichiki, Yuki Sato, Masutaka Furue, Yasuharu Nakashima, Yoshinao Oda

Anticancer Research 40 ( 11 ) 6221 - 6228 2020.11

Publishing type：Research paper (scientific journal)

© 2020 International Institute of Anticancer Research. All rights reserved. Background/aim: Malignant peripheral nerve sheath tumor (MPNST) is a rare soft-tissue tumor, and its diagnosis is usually made histopathologically. The effectiveness of chemotherapy and radiotherapy has not been established. We elucidated prognostic factors, diagnostic markers, and therapeutic targets. Materials and Methods: Cases of MPNST were studied using next-generation sequencing. A total of 24 tumor samples, 11 from von Recklinghausen’s disease-associated MPNST (vRH-MPNST), 11 from sporadic non-vRH MPNST, and two neurofibroma (NF) cases were retrieved, on which next-generation sequencing and survival analysis were performed. Results: We identified NF1 gene mutations, including three mutations in two NFs, and 10 mutations in eight MPNSTs (five vRHMPNSTs and three sporadic MPNSTs). Meningioma 1 (MN1) gene alteration was detected in six cases of vRH-MPNST. It is considered that MN1 gene alteration is related to the tumorigenesis of vRH-MPNST. Conclusion: MN1 gene mutation was detected in more than half of our cases, it may have potential for use as a therapeutic target in vRH-MPNST.

DOI： 10.21873/anticanres.14642

B cell receptor signaling related to resistance to Helicobacter pylori eradication therapy in gastric diffuse large B cell lymphoma. Reviewed International journal

Takehiro Torisu, Shinichi Kawano, Kohta Miyawaki, Hidetaka Yamamoto, Yutaro Ihara, Yuichi Matsuno, Kumiko Torisu, Takeshi Sugio, Kensuke Sasaki, Takashi Shimakawa, Koji Kato, Koichi Akashi, Shotaro Nakamura, Takanari Kitazono

Hematological oncology 39 ( 1 ) 145 - 147 2020.10

PD-L1 and IDO1 expression and tumor-infiltrating lymphocytes in osteosarcoma patients: comparative study of primary and metastatic lesions Reviewed International journal

Yu Toda, Kenichi Kohashi, Yuichi Yamada, Masato Yoshimoto, Shin Ishihara, Yoshihiro Ito, Takeshi Iwasaki, Hidetaka Yamamoto, Yoshihiro Matsumoto, Yasuharu Nakashima, Masaaki Mawatari, Yoshinao Oda

Journal of Cancer Research and Clinical Oncology 146 ( 10 ) 2607 - 2620 2020.10

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

© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: Programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) are immunosuppressive proteins known to be associated with poor prognosis in various cancers. However, their expression and clinical relevance in osteosarcoma remain unknown. In this study, the relationships of PD-L1 and IDO1 expression with clinicopathological features and prognosis were explored. Methods: The expression of PD-L1, IDO1, CD3, CD4, and CD8 in 112 formalin-fixed, paraffin-embedded tumor tissues collected by biopsy or surgical resection from 56 osteosarcoma patients was evaluated immunohistochemically. Moreover, four osteosarcoma cell lines were evaluated for the effects of IFNγ on PD-L1 and IDO1 mRNA expression by real-time reverse-transcription polymerase chain reaction. Results: In pre-neoadjuvant chemotherapy (NAC) primary specimens, 10 cases (17%) showed PD-L1 expression and 12 (21%) showed IDO1 expression. Six of ten cases (60%) with PD-L1 positivity co-expressed IDO1. In post-NAC metastatic lesions, the frequency of immunoexpression of PD-L1 and IDO1 was increased compared with that in pre-NAC specimens. PD-L1 and/or IDO1 expression was not associated with poor prognosis. PD-L1 immunoexpression was significantly associated with the infiltration of CD3+ T cells, CD4+ T cells, and CD8+ T cells; while, IDO1 immunoexpression was significantly associated with the infiltration of CD3+ T cells and CD4+ T cells. In all osteosarcoma cell lines, PD-L1 and IDO1 expression was upregulated by stimulation with IFNγ. Conclusion: Our results suggest that the PD-L1 and IDO1 immune checkpoint inhibitors may provide clinical benefit in osteosarcoma patients with metastatic lesions after conventional chemotherapy.

DOI： 10.1007/s00432-020-03242-6

The impact of clinicopathological factors on clinical outcomes in patients with salivary gland adenoid cystic carcinoma: a multi-institutional analysis in Japan. Reviewed

Daisuke Kawakita, Takayuki Murase, Kaori Ueda, Satoshi Kano, Yuichiro Tada, Kiyoaki Tsukahara, Kenji Okami, Tetsuro Onitsuka, Yasushi Fujimoto, Takuma Matoba, Kazuo Sakurai, Toru Nagao, Nobuhiro Hanai, Ryo Kawata, Naohito Hato, Ken-Ichi Nibu, Makoto Urano, Ken-Ichi Taguchi, Masato Nakaguro, Kimihide Kusafuka, Hidetaka Yamamoto, Toshitaka Nagao, Hiroshi Inagaki

International journal of clinical oncology 25 ( 10 ) 1774 - 1785 2020.10

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

BACKGROUND: Owing to the low incidence of adenoid cystic carcinoma (AdCC), reliable survival estimates and prognostic factors remained unclarified. METHODS: In this multi-institutional retrospective analysis, we collected 192 AdCC cases, and investigated the impact of clinicopathological factors on clinical outcomes of the patients. All AdCC cases were of salivary gland origin and were surgically treated with curative intent. Diagnoses of AdCC were validated by a central pathology review by expert pathologists. RESULTS: The 5-year overall survival (OS) and disease-free survival (DFS) rates were 92.5 and 50.0%, respectively. Treatment failure occurred in 89 patients (46%) with the distant failures in 65 (34%). Multivariate analysis indicated that pN2 and a pathologically positive surgical margin were independent prognostic factors for both OS and DFS. Histological grade III was an independent prognostic factor for OS. A primary site in the submandibular gland, pT3/4, pN1, and histological grade II were independent prognostic factors for DFS. Postoperative radiation therapy (PORT) improved the locoregional control (LRC) rate. Prophylactic neck dissection was not associated with a better OS or better LRC among patients with cN0. Facial nerve dissection did not improve clinical outcomes in parotid AdCC cases without facial nerve palsy. CONCLUSIONS: A higher TN classification, a pathologically positive surgical margin, and a higher histological grade were associated with a lower OS. PORT improved LRC rates but neck dissection failed to improve clinical outcomes in patients with cN0. As the distant metastasis was frequent, effective systemic therapy is imperative to improve the survival of AdCC patients.

DOI： 10.1007/s10147-020-01731-9

Benign mesenteric lipomatous tumor in a child: a case report and literature review. Reviewed International journal

Naoki Hashizume, Takato Aiko, Suguru Fukahori, Shinji Ishii, Nobuyuki Saikusa, Yoshinori Koga, Naruki Higashidate, Saki Sakamoto, Shiori Tsuruhisa, Hirotomo Nakahara, Hiroko Muta, Hiroaki Miyoshi, Yoshiki Naito, Hidetaka Yamamoto, Yoshinao Oda, Yoshiaki Tanaka, Minoru Yagi

Surgical case reports 6 ( 1 ) 243 - 243 2020.9

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

BACKGROUND: Lipomatous tumors are the most common type of soft-tissue tumors. Benign lipomatous tumors are lipomas and lipoblastoma. We herein report a case of benign mesenteric lipomatous tumor and the largest collection of known benign mesenteric lipomatous tumors in children in the literature. CASE PRESENTATION: A 3-year-old girl presented with repeated dull abdominal pain and left abdominal mass swelling. On a physical examination, the child had a soft, moderately distended left abdomen that was not tender when palpated. Computed tomography and magnetic resonance imaging demonstrated a large fatty mass within the mesentery, measuring approximately 8 × 6 cm. The mass extended from the right upper quadrant to the lower pole of the kidneys. Laparotomy with resection of the mesenteric tumor was performed under general anesthesia. A well-capsuled tumor was a soft, yellow mass and found loosely attached to the mesenterium of the ileum. A histopathological examination demonstrated the lobular proliferation of mature adipocytes. Atypical lipoblasts were not seen. These features are compatible with benign lipomatous tumor, such as lipoma or lipoblastoma with maturation. CONCLUSION: In conclusion, benign mesenteric lipomatous tumors tend to be large in size over 10 cm in longitudinal length. However, resection is well tolerated in the vast majority of cases with benign post-operative courses.

DOI： 10.1186/s40792-020-01020-7

Plasmablastic lymphoma occurring in the vicinity of enterocutaneous fistula in Crohn's disease. Reviewed International journal

Seisho Sato, Makiko Nakahara, Koji Kato, Tomohiko Moriyama, Sae Utsumi, Kensuke Sasaki, Takahiro Shima, Hiroaki Miyoshi, Hidetaka Yamamoto, Masutaka Furue

The Journal of dermatology 47 ( 12 ) e442-e443 2020.9

Amide proton transfer (APT) imaging of parotid tumors: Differentiation of malignant and benign tumors. Reviewed International journal

Takeshi Kamitani, Koji Sagiyama, Osamu Togao, Yuzo Yamasaki, Tomoyuki Hida, Yuko Matsuura, Yuriko Murayama, Ryuji Yasumatsu, Hidetaka Yamamoto, Hidetake Yabuuchi

European journal of radiology 129 109047 - 109047 2020.8

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

PURPOSE: To assess the usefulness of amide proton transfer (APT) imaging in differentiating parotid tumors. MATERIAL AND METHODS: We retrospectively analyzed 43 histopathologically proven parotid solid tumors with diameters ≥2 cm. Twenty-one tumors were benign and 12 tumors were malignant. Two-dimensional APT imaging was performed using a saturation pulse with a duration of 2 s and a saturation power level of 2 μT. For acquiring Z-spectra, the imaging was repeated at 25 saturation frequency offsets from ω = -6 to +6 ppm with a step of 0.5 ppm as well as one scan acquired far off-resonance (-1560 ppm) for signal normalization. For the APT imaging, the asymmetry analysis at 3.5 ppm downfield from the water signal was calculated. The mean APT signal intensity (SI) was compared between the benign and malignant tumors. RESULTS: The mean APT SI was 2.23 ± 0.80 % in the benign tumors and significantly higher at 2.99 ± 0.99 % in the malignant tumors (P = 0.01). A receiver operating curve analysis revealed that the optimal APT SI threshold was 2.40 for distinguishing malignant tumors from benign tumors with an area under the curve of 0.74. The sensitivity, specificity, and accuracy were 83.3%, 61.3%, and 67.4%, respectively. CONCLUSION: The mean APT SI of the malignant parotid tumors was significantly higher than that of the benign parotid tumors.

DOI： 10.1016/j.ejrad.2020.109047

Central pathology review of salivary gland adenoid cystic carcinoma. Reviewed International journal

Kaori Ueda, Takayuki Murase, Toshitaka Nagao, Kimihide Kusafuka, Makoto Urano, Hidetaka Yamamoto, Masato Nakaguro, Ken-Ichi Taguchi, Ayako Masaki, Hideaki Hirai, Daisuke Kawakita, Kiyoaki Tsukahara, Naohito Hato, Toru Nagao, Yasushi Fujimoto, Kazuo Sakurai, Nobuhiro Hanai, Satoshi Kano, Tetsuro Onitsuka, Kenji Okami, Ken-Ichi Nibu, Yuichiro Tada, Ryo Kawata, Hiroshi Inagaki

Head & neck 42 ( 8 ) 1721 - 1727 2020.8

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

BACKGROUND: To assess the role of a central pathology review in the diagnosis of salivary gland adenoid cystic carcinoma (AdCC). METHODS: Surgically resected salivary gland tumors diagnosed as AdCC (n = 219) in 15 reference hospitals in Japan were subjected to a retrospective pathological re-evaluation. RESULTS: After the review, the AdCC diagnosis was revised in 21/219 cases (9.6%). The six benign tumors (2.7%) comprised five basal cell adenomas and one pleomorphic adenoma, and among these six patients, three received postoperative radiotherapy. The remaining 15 malignant tumors (6.8%) comprised nine basal cell adenocarcinomas and six other carcinomas. All revised basal cell adenoma/adenocarcinoma cases were of rare cribriform variants. CONCLUSIONS: A significant proportion of AdCC pathology reports were revised after the central pathology review. It should be emphasized that the greatest attention should be paid in differentiating AdCC from cribriform variant basal cell adenoma/adenocarcinoma, which is very rare in salivary gland tumors.

DOI： 10.1002/hed.26081

Genetic landscape of external auditory canal squamous cell carcinoma. Reviewed International journal

Kuniaki Sato, Noritaka Komune, Takahiro Hongo, Kensuke Koike, Atsushi Niida, Ryutaro Uchi, Teppei Noda, Ryunosuke Kogo, Nozomu Matsumoto, Hidetaka Yamamoto, Muneyuki Masuda, Yoshinao Oda, Koshi Mimori, Takashi Nakagawa

Cancer science 111 ( 8 ) 3010 - 3019 2020.6

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

External auditory canal squamous cell carcinoma (EACSCC) is an extremely rare and aggressive malignancy. Due to its rarity, the molecular and genetic characteristics of EACSCC have not yet been elucidated. To reveal the genetic alterations of EACSCC, we performed whole exome sequencing (WES) on 11 primary tumors, 1 relapsed tumor and 10 noncancerous tissues from 10 patients with EACSCC, including 1 with a rare case of synchronous bilateral EACSCC of both ears. WES of the primary tumor samples showed that the most frequently mutated gene is TP53 (63.6%). In addition, recurrent mutations in CDKN2A, NOTCH1, NOTCH2, FAT1 and FAT3 were detected in multiple samples. The mutational signature analysis of primary tumors indicated that the mutational processes associated with the activation of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) deaminases are the most common in EACSCC, suggesting its similarity to SCC from other primary sites. Analysis of arm-level copy number alterations detected notable amplification of chromosomes 3q, 5p and 8q as well as deletion of 3p across multiple samples. Focal chromosomal aberrations included amplifications of 5p15.33 (ZDHHC11B) and 7p14.1 (TARP) as well as deletion of 9p21.3 (CDKN2A/B). The protein expression levels of ZDHHC11B and TARP in EACSCC tissues were validated by immunohistochemistry. Moreover, WES of the primary and relapsed tumors from a case of synchronous bilateral EACSCC showed the intrapatient genetic heterogeneity of EACSCC. In summary, this study provides the first evidence for genetic alterations of EACSCC. Our findings suggest that EACSCC mostly resembles other SCC.

DOI： 10.1111/cas.14515

Signet Ring Cell Differentiation in Salivary Duct Carcinoma with Rhabdoid Features: Report of Three Cases and Literature Review. Reviewed International journal

Mayumi Akaki, Akira Ishihara, Kentaro Nagai, Hidekazu Naono, Kenichi Taguchi, Hidetaka Yamamoto, Hiroyuki Tanaka, Hiroaki Kataoka

Head and neck pathology 15 ( 1 ) 341 - 351 2020.6

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

Salivary duct carcinoma with rhabdoid features (SDCRF) is a rare salivary tumor with poor prognosis and is proposed as a salivary counterpart of pleomorphic lobular carcinoma of the breast (PLCB). Here, we report three cases of SDC with rhabdoid features (SDCRF) mimicking PLCB. Pleomorphic adenoma (PA) component was accompanied in all the cases confirming carcinoma ex PA. One patient had frequent rhabdoid features and showed invasive growth into the surrounding tissue. The other two patients had intracapsular tumor but with rhabdoid features. The patients with intracapsular SDCRF survived for > 5 years after surgery with no evidence of recurrence, whereas the patient with extracapsular SDCRF died 10 months after biopsy, and autopsy revealed disseminated metastasis to the central nervous system. Histologically, tumor cells in all three cases resembled PLCB, with a discohesive appearance, abundant cytoplasm, enlarged hyperchromatic nuclei, and similar immunohistochemical profiles, namely loss of membranous E-cadherin, obscured expression of membranous β-catenin, diffuse positivity of androgen receptor, gross cystic disease fluid protein-15, mitochondrial adenosine triphosphate synthase subunit β, MUC1, and INI-1. Estrogen and progesterone receptors were negative, and HER2 immunoreactivities were variable. The tumor cells of extracapsular invasive SDCRF exhibited higher MIB-1 labeling index and more frequent intracytoplasmic lumina than those of intracapsular SDCRF. Ultrastructurally, rhabdoid cells contained intracytoplasmic lumina with microvillous structure, analogous to those reported in PLCB. No intracytoplasmic intermediate filament aggregation was observed. These observations indicate that SDCRF is a salivary counterpart of PLCB and under signet ring cell differentiation.

DOI： 10.1007/s12105-020-01186-4

Retroperitoneal Myxofibrosarcoma: A Controversial Entity. Reviewed International journal

Masato Yoshimoto, Yuichi Yamada, Shin Ishihara, Kenichi Kohashi, Yu Toda, Yoshihiro Ito, Yosuke Susuki, Izumi Kinoshita, Hidetaka Yamamoto, Yasuharu Nakashima, Yoshinao Oda

Pathology, research and practice 216 ( 6 ) 152969 - 152969 2020.6

Primary bone anaplastic large cell lymphoma of lymphohistiocytic variant, ALK-negative: A challenging diagnosis. Reviewed International journal

Kennosuke Karube, Norihiro Nakada, Hidetaka Yamamoto

Pathology international 70 ( 6 ) 376 - 378 2020.6

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