Faculty Profiles - YAMAMOTO HIDETAKA

Papers - YAMAMOTO HIDETAKA

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Histological and immunohistochemical features and genetic alterations in the malignant progression of giant cell tumor of bone: a possible association with TP53 mutation and loss of H3K27 trimethylation. International journal

Shin Ishihara, Hidetaka Yamamoto, Takeshi Iwasaki, Yu Toda, Takeo Yamamoto, Masato Yoshimoto, Yoshihiro Ito, Yousuke Susuki, Kengo Kawaguchi, Izumi Kinoshita, Yuichi Yamada, Kenichi Kohashi, Toshifumi Fujiwara, Nokitaka Setsu, Makoto Endo, Yoshihiro Matsumoto, Yuko Kakuda, Yasuharu Nakashima, Yoshinao Oda

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 35 ( 5 ) 640 - 648 2022.5

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

In rare cases, giant cell tumor of bone (GCTB) can undergo primary or secondary malignant transformation to malignant giant cell tumor of bone (MGCTB), but the details of the molecular alterations are still unclear. The present study aimed to elucidate the clinicopathologic and molecular features of MGCTBs based on immunohistochemistry, fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) of nine MGCTBs (five primary and four secondary). Seven (78%) of 9 MGCTBs were immunohistochemically positive for H3.3 G34W. In two (22%) patients, although GCTB components were focally or diffusely positive for H3.3 G34W, their malignant components were entirely negative for H3.3 G34W, which was associated with heterozygous loss of H3F3A by FISH. NGS on four MGCTBs revealed pathogenic mutations in TP53 (n = 3), EZH2 (n = 1) and several other genes. Immunohistochemical analysis of the nine MGCTBs confirmed the p53 nuclear accumulation (n = 5) and loss of H3K27me3 expression (n = 3) and showed that they were mutually exclusive. In addition, four (80%) of five cases of pleomorphic or epithelioid cell-predominant MGCTBs were positive for p53, while three (75%) of four cases of spindle cell-predominant MGCTBs were negative for trimethylation at lysine 27 of histone 3 (H3K27me3). The results suggested that p53 alteration and dysfunction of histone methylation as evidenced by H3K27me3 loss may play an important role in the malignant progression of GCTB, and might contribute to the phenotype-genotype correlation in MGCTB. The combined histologic, immunohistochemical and molecular information may be helpful in part for the diagnosis of challenging cases.

DOI： 10.1038/s41379-021-00972-x

Cyclin-dependent kinase 8 is an independent prognosticator in uterine leiomyosarcoma. International journal

Nobuko Yasutake, Takeshi Iwasaki, Hidetaka Yamamoto, Kenzo Sonoda, Keisuke Kodama, Kaoru Okugawa, Kazuo Asanoma, Hideaki Yahata, Kiyoko Kato, Yoshinao Oda

Pathology, research and practice 235 153920 - 153920 2022.4

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

Cyclin-dependent kinase 8 (CDK8) is associated with the transcriptional mediator complex and regulates several transcription factors implicated in cancer. CDK8 expression is a poor prognostic marker in colon and breast cancer by immunohistochemistry. However, somatic mutations in exon 2 of the RNA polymerase II transcriptional mediator subunit MED12 occur in 7-30% of cases of uterine leiomyosarcoma (ULMS), suggesting that these alterations contribute to tumorigenesis. Public genomic mutation data of 80 patients with ULMS were used for MED12 and CDK8 mutation analysis. The expression of MED12, CDK8 and β-catenin was evaluated by immunohistochemistry in our cohort of 60 patients with ULMS, in addition with MED12 mutation status and survival stage. Univariate analysis was performed using the log-rank test, and Cox regression was used to identify independent prognostic factors. Multivariate Cox regression analysis revealed that advanced stage (p < 0.0001) and high CDK8 expression (p = 0.0014) were independent predictors of poor prognosis. MED12 mutation status was not signiﬁcantly associated with CDK8 expression (p = 0.6873) and DSS (p = 0.8075). In conclusion, our data suggest that CDK8 expression may identify a subset of ULMS patients with a poor prognosis.

DOI： 10.1016/j.prp.2022.153920

Clinical, Radiological, and Histopathological Characteristics of Periosteal Chondrosarcoma with a Focus on the Frequency of Medullary Invasion. International journal

Makoto Nakagawa, Makoto Endo, Yosuke Susuki, Nobuhiko Yokoyama, Akira Maekawa, Akira Nabeshima, Keiichiro Iida, Toshifumi Fujiwara, Nokitaka Setsu, Tomoya Matsunobu, Yoshihiro Matsumoto, Ryohei Yokoyama, Yuichi Yamada, Kenichi Kohashi, Hidetaka Yamamoto, Yoshinao Oda, Yukihide Iwamoto, Yasuharu Nakashima

Journal of clinical medicine 11 ( 7 ) 2022.4

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

Periosteal chondrosarcoma is an extremely rare malignant cartilage-forming tumour that originates from the periosteum and occurs on the surface of bone. Often, it is difficult to distinguish periosteal chondrosarcoma from other tumours, and reports in the literature are scarce. This study aims to investigate the characteristics of periosteal chondrosarcoma, focusing particularly on medullary invasion. Among 33 periosteal cartilaginous tumours, seven patients with pathologically proven periosteal chondrosarcoma were identified retrospectively. The average tumour size was 5.4 cm in the long axis; two tumours were smaller than 3.0 cm. Six tumours were resected with a wide margin, and the remaining tumour had a marginal margin. Histology revealed that six tumours (85.7%) had invaded the medullary cavity; three of these did not show invasion into the medullary cavity on MRI evaluation. Neither local recurrence nor metastasis was observed among these patients. The frequency of invasion of the medullary cavity was higher than that reported previously. The recommended treatment for periosteal chondrosarcoma is resection with an adequate margin. Therefore, surgeons should consider the possibility of medullary invasion when attempting to achieve a histologically negative margin, even if the tumour does not show invasion into the medullary cavity on MRI.

DOI： 10.3390/jcm11072062

Myxoid type and non-myxoid type of intimal sarcoma in large vessels and heart: review of histological and genetic profiles of 20 cases. International journal

Yuichi Yamada, Izumi Kinoshita, Yoshiko Miyazaki, Yuki Tateishi, Yusuke Kuboyama, Takeshi Iwasaki, Kenichi Kohashi, Hidetaka Yamamoto, Shin Ishihara, Yu Toda, Yoshihiro Ito, Yosuke Susuki, Kengo Kawaguchi, Mikiko Hashisako, Yui Yamada-Nozaki, Daisuke Kiyozawa, Taro Mori, Takeo Yamamoto, Kenji Tsuchihashi, Kazumi Kuriwaki, Munenori Mukai, Masataka Kawai, Keiko Suzuki, Hirotake Nishimura, Kenji Bando, Junya Masumoto, Mana Fukushima, Junichi Motoshita, Hiroki Mori, Akira Shiose, Yoshinao Oda

Virchows Archiv : an international journal of pathology 480 ( 4 ) 919 - 925 2022.4

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

Intimal sarcoma is one of the most common and well-known primary malignant neoplasms of the aorta and heart. The authors reviewed cases of intimal sarcoma from histological, immunohistochemical and genetic perspectives. Twenty cases of intimal sarcoma were retrieved. Immunohistochemistry and FISH of MDM2 and PDGFRA genes were performed. All 20 tumours were composed of spindle-shaped, stellate, oval or polygonal tumour cells with irregular hyperchromatic nuclei arranged in a haphazard pattern, accompanied by nuclear pleomorphism and frequent mitotic figures. Other histological findings were as follows: abnormal mitosis in 10 cases (50%), necrosis in 15 cases (75%), myxoid stroma in 12 cases (60%), cartilaginous formation in 1 case (5%), haemorrhage in 12 cases (60%) and fibrinous deposition in 14 cases (70%). The tumours were positive for MDM2 in 16 cases (80%), ERG in 4 cases (20%), alpha-smooth muscle actin in 6 cases (30%), desmin in 5 cases (25%) and AE1/AE3 in 4 cases (20%). Immunohistochemical positivity was focal in each case. Loss of H3K27me3 expression was noted in 2 cases (10%). MDM2 and PDGFRA gene amplifications were detected in 11 cases (55%) and 1 case (5%), respectively. Fisher's exact test revealed a significant correlation between MDM2 gene amplification and myxoid stroma (p = 0.0194). No parameters showed any association with the anatomical location of the tumours. It was suggested that myxoid histology of intimal sarcoma may be associated with MDM2 gene amplification and that intimal sarcoma may be divided into myxoid and non-myxoid types.

DOI： 10.1007/s00428-022-03293-9

Retrospective Study of Cisplatin/Carboplatin, 5-Fluorouracil Plus Cetuximab (EXTREME) for Advanced-stage Salivary Gland Cancer

Takafumi Nakano, Ryuji Yasumatsu, Kazuki Hashimoto, Ryosuke Kuga, Takahiro Hongo, Hidetaka Yamamoto, Mioko Matsuo, Takahiro Wakasaki, Rina Jiromaru, Tomomi Manako, Satoshi Toh, Muneyuki Masuda, Moriyasu Yamauchi, Yuichiro Kuratomi, Hideoki Uryu, Torahiko Nakashima, Akihiro Tamae, Risa Tanaka, Masahiko Taura, Toranoshin Takeuchi, Takamasa Yoshida, Takashi Nakagawa

In vivo (Athens, Greece) 36 ( 2 ) 979 - 984 2022.3

Publishing type：Research paper (scientific journal)

BACKGROUND/AIM: Surgery remains the standard treatment for salivary gland carcinoma (SGC). Our study investigated the association between epidermal growth factor receptor (EGFR) status in recurrent/metastatic SGC and the effectiveness of treatment with cisplatin/carboplatin and 5-fluorouracil plus cetuximab (EXTREME). PATIENTS AND METHODS: We retrospectively collected 19 SGCs from patients treated with the EXTREME regimen. After analyzing EGFR expression and gene copy number gain, we evaluated the correlation between EGFR status and clinicopathological factors and prognosis. RESULTS: EGFR overexpression was detected in 77.8% cases, but not statistically associated with clinicopathological factors or prognosis. EGFR gene copy number gain was detected in 16.7% cases, and statistically positively correlated with lymph node metastasis (p=0.0291). The best overall response was partial response in two cases, stable disease in 15, and progressive disease in one case. The EXTREME regimen was discontinued in all cases. CONCLUSION: Our results suggest that SGCs are positive for EGFR protein expression but the response rate to the EXTREME regimen was unremarkable.

DOI： 10.21873/invivo.12790

Salivary mucoepidermoid carcinoma: histological variants, grading systems, CRTC1/3-MAML2 fusions, and clinicopathological features. International journal

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

Histopathology 80 ( 4 ) 729 - 735 2022.3

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

AIMS: To investigate the histological diversity of salivary mucoepidermoid carcinoma (MEC), its clinicopathological features, and its associations with CRTC1/3-MAML2 fusions. METHODS AND RESULTS: Salivary MEC cases (n = 177) were examined for CRTC1/3-MAML2 fusions, histological variants were classified, and tumours were graded according to four different grading systems. Adverse histological features considered to be unusual in MEC were also investigated. Of the 177 MEC cases, 110 were positive for CRTC1/3-MAML2 fusions. The classical variant was the most frequent in the fusion-positive case group, the fusion-negative case group, and the total case group. The clear/oncocytic variant was the second most frequent in the fusion-positive and total case groups. Oncocytic, Warthin-like and spindle variants were seen in the fusion-positive case group only. Clear cell, sclerosing, mucinous and central variants were seen in both the fusion-positive case group and the fusion-negative case group. No case was classified as a ciliated variant, as a mucoacinar variant, or as a high-grade transformation. As compared with the classical variant, non-classical variants were characterised by frequent CRTC1/3-MAML2 fusions and a low clinical stage in all cases. Of the four histological features considered to be unusual in MEC, marked nuclear atypia, frequent mitoses (>10/10 high-power fields) and extensive necrosis were found independently of the fusion status, and were present in 3-5% of all cases. However, none of the cases showed overt keratinisation. On comparison, the Armed Forces Institute of Pathology and modified Healey grading systems downgraded tumours, the Brandwein system upgraded tumours, and the Memorial Sloan Kettering system provided a moderate means of assessment. CONCLUSION: Recognition of the histological diversity of MEC, its clinicopathological features and its associations with CRTC1/3-MAML2 fusions is helpful for an accurate diagnosis of this carcinoma.

DOI： 10.1111/his.14586

Treatment Efficacy of PD-1 Inhibitor Therapy in Patients With Recurrent and/or Metastatic Salivary Gland Carcinoma. International journal

Kazuki Hashimoto, Ryuji Yasumatsu, Ryosuke Kuga, Takahiro Hongo, Hidetaka Yamamoto, Mioko Matsuo, Takahiro Wakasaki, Rina Jiromaru, Tomomi Manako, Satoshi Toh, Muneyuki Masuda, Moriyasu Yamauchi, Yuichiro Kuratomi, Hideoki Uryu, Torahiko Nakashima, Akihiro Tamae, Risa Tanaka, Masahiko Taura, Toranoshin Takeuchi, Takamasa Yoshida, Takashi Nakagawa

Anticancer research 42 ( 2 ) 981 - 989 2022.2

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

BACKGROUND/AIM: The efficacy of programmed cell death 1 (PD-1) inhibitor therapy for patients with recurrent and/or metastatic salivary gland carcinoma (R/M SGC) remains unclear. PATIENTS AND METHODS: We retrospectively analyzed 36 patients with R/M SGC treated with PD-1 inhibitor. The expression of programmed cell death ligand 1 (PD-L1) and mismatch repair (MMR) proteins was also analyzed. RESULTS: The objective response rate (ORR) was 11.1%. The histopathological subtypes of patients who achieved complete response or partial response were salivary duct carcinoma (SDC) in three patients and poorly differentiated carcinoma in one patient, all of whom showed a positive PD-L1 expression. The expression of MMR proteins was not associated with the efficacy of PD-1 inhibitors. CONCLUSION: Although the efficacy of PD-1 inhibitor therapy in R/M SGC is limited, certain patients may respond and achieve long-term disease control. There is a potential therapeutic effect in SDC patients with positive PD-L1 expression.

DOI： 10.21873/anticanres.15558

Lymphoid and myeloid proliferative disorders associated with inflammatory bowel disease: a clinicopathological study of 15 cases. International journal

Yoshifumi Hori, Hidetaka Yamamoto, Shinichiro Kawatoko, Yui Nozaki, Takehiro Torisu, Koji Kato, Yuhki Koga, Hiroaki Miyoshi, Koichi Ohshima, Yuki Tateishi, Shotaro Nakamura, Takanari Kitazono, Yoshinao Oda

Human pathology 120 88 - 98 2022.2

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

Lymphoproliferative disorder (LPD) can occur in patients with inflammatory bowel disease (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). On rare occasions, patients with IBD develop myeloid neoplasms; however, the frequency and clinicopathological features of IBD-associated lymphoid and myeloid proliferative disorder (LMPD) in Japanese patients are still unclear. In this study, we reviewed 2474 Japanese patients with IBD and found that LMPD occurred in 12 (0.5%) patients with UC (n = 7) or CD (n = 5). Together with an additional 3 cases, we analyzed a total of 15 cases of LMPD for clinicopathological and histological features. Based on the status of using immunosuppressants such as biologics and immunomodulators, Epstein-Barr virus (EBV) infection, and histopathology, the 15 cases were classified into Group I (high-grade LPD; n = 7), Group II (low-grade LPD; n = 5), and Group III (myeloid neoplasms; n = 3). Most patients in Group I were undergoing strong immunosuppressive therapy, and the LPD lesions corresponded to high-grade B-cell or T cell/natural killer cell lymphoma often with EBV infection. Discontinuation of immunosuppressive drugs alone did not resolve these LPDs; Group I patients required chemotherapy, and eventually 4 of them (57%) died of the tumor. Most cases in Group II were low-grade B-cell lymphoma without EBV infection and had an indolent clinical course with excellent prognosis. All patients in Group III developed acute myeloid leukemia (AML) during the course of CD. Two (67%) of these patients died of AML. Our study suggests that IBD-associated LMPD is very rare but can follow an aggressive clinical course.

DOI： 10.1016/j.humpath.2021.12.010

Clinicopathological and histopathological review of dedifferentiated liposarcoma: a comprehensive study of 123 primary tumours. International journal

Taro Mori, Yuichi Yamada, Izumi Kinoshita, Kenichi Kohashi, Hidetaka Yamamoto, Yoshihiro Ito, Yosuke Susuki, Kengo Kawaguchi, Yasuharu Nakashima, Yoshinao Oda

Histopathology 80 ( 3 ) 538 - 557 2022.2

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

AIMS: Dedifferentiated liposarcoma (DDLS) has varying histopathological features, but their significance for the biological behaviour of this disease has not been fully clarified. The aim of this study was to elucidate the prognostic factors for DDLS by clinicopathologically reviewing a large case series. METHODS AND RESULTS: We clinicopathologically reviewed 123 cases of primary de-novo DDLS without preoperative treatment, including 81 in the internal trunk (internal DDLS) and 42 in peripheral sites (peripheral DDLS). Univariate and multivariate analyses of their features were also performed for all cases, the internal DDLS group, and the peripheral DDLS group. The results showed that, in all three groups, distant metastasis was significantly associated with shorter overall survival (OS) (univariate analysis, P < 0.0001, P = 0.0011, and P = 0.0101, respectively), whereas local recurrence showed no significant effect on prognosis. Histopathologically, a high mitotic count and the presence of round tumour cells were significantly associated with shorter OS in multivariate analysis of the internal DDLS group [respectively: P = 0.0022, hazard ratio (HR) 4.39, 95% confidence interval (CI) 1.71-11.28; and P = 0.0014, HR 7.19, 95% CI 2.14-24.16]. In the peripheral DDLS group, necrosis and high-grade histological components were significantly associated with shorter OS (univariate analysis, P = 0.0068 and P = 0.0174, respectively). CONCLUSIONS: The presence of round tumour cells may be one of the histological factors associated with a worse prognosis of DDLS patients, as previous studies indicated. This study also suggests that distant metastasis may be predictive of prognosis for both internal and peripheral DDLS, rather than local recurrence.

DOI： 10.1111/his.14588

High-risk HPV-related Squamous Cell Carcinoma in the Conjunctiva and Lacrimal sac: Clinicopathologic Characteristics and Diagnostic Utility of p16 and Rb Immunohistochemistry. International journal

Takahiro Hongo, Hidetaka Yamamoto, Mika Tanabe, Ryuji Yasumatsu, Ryosuke Kuga, Yoshiko Miyazaki, Rina Jiromaru, Kazuki Hashimoto, Yuki Tateishi, Koh-Hei Sonoda, Takashi Nakagawa, Yoshinao Oda

The American journal of surgical pathology 46 ( 7 ) 977 - 987 2022.1

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

High-risk human papillomavirus (HPV) infection in conjunctival and lacrimal sac squamous cell carcinomas (SCCs) has been sporadically reported; however, its prevalence, clinicopathologic significance and surrogate markers have not been fully elucidated. Here, we attempted to clarify these questions in Japanese patients with conjunctiva and lacrimal sac SCCs. We retrospectively collected 51 conjunctival SCC and 7 lacrimal sac SCC samples and analyzed them for (1) transcriptionally active high-risk HPV infection using messenger RNA in situ hybridization and (2) protein expressions of p16 and Rb using immunohistochemistry (IHC). Among a total of 58 cases, 25 (43.1%) and 16 (27.6%) tumors were positive for p16-IHC and HPV in situ hybridization, respectively. Ten (19.6%) of the 51 conjunctival SCCs, especially in the palpebral conjunctiva, and 6 (85.7%) of the 7 lacrimal sac SCCs were positive for high-risk HPV. High-risk HPV infection was significantly associated with younger patients, nonkeratinizing SCC histology, p16-positivity and partial loss of Rb expression, but not with recurrence risk. Notably, p16-IHC was not a perfect surrogate marker for high-risk HPV infection; only 64% (16/25) of p16-positive tumors were positive for high-risk HPV. In contrast, the p16+/Rb partial loss pattern was exclusively correlated with high-risk HPV-positivity. The results suggest that the combination of p16 and Rb expression patterns by IHC could be a useful method to predict high-risk HPV infection in conjunctival and lacrimal sac SCCs. HPV infection may be of less prognostic value in this field of cancers.

DOI： 10.1097/PAS.0000000000001857

An Analysis of 20 Cases of Radiation-Associated Sarcoma, Including 4 Cases Treated by Carbon Ion Radiotherapy. International journal

Takahito Negishi, Akira Matsunobu, Makoto Endo, Ryouhei Yokoyama, Shuhei Kusano, Nobuki Furubayashi, Kenichi Taguchi, Yoshiyuki Shioyama, Keiichiro Iida, Toshifumi Fujiwara, Nokitaka Setsu, Yoshihiro Matsumoto, Yasuharu Nakashima, Kenichi Kohashi, Hidetaka Yamamoto, Yoshinao Oda, Motonobu Nakamura

Oncology 100 ( 3 ) 148 - 154 2022

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

INTRODUCTION: Radiation-associated sarcoma (RAS) is one of the most life-threatening complications associated with the treatment of malignant neoplasms. Because all RAS patients have a history of radiotherapy, there have been no effective treatment options when RAS is not completely resected. METHODS: We retrospectively reviewed 20 RAS patients, including 4 unresectable cases treated by carbon ion radiotherapy (CIRT). RESULTS: The primary diseases targeted by radiotherapy included malignant lymphoma (n = 4), cervical cancer (n = 3), pharyngeal cancer (n = 3), breast cancer (n = 2), lung cancer (n = 1), rectal cancer (n = 1), maxillary cancer (n = 1), synovial sarcoma (n = 1), and benign neoplasms (n = 4). The histological diagnoses of RAS included osteosarcoma (n = 8), leiomyosarcoma (n = 3), undifferentiated pleomorphic sarcoma (n = 3), rhabdomyosarcoma (n = 1), angiosarcoma (n = 1), malignant peripheral nerve sheath tumor (n = 1), spindle cell sarcoma NOS (n = 1), and sarcoma not further specified (n = 2). The median survival time from the diagnosis of RAS was 26 months. Eleven patients underwent surgery. Five of these patients achieved a continuous disease free (CDF) status or showed no evidence disease. Four patients underwent CIRT. One of these patients with leiomyosarcoma achieved a CDF status, and the other patient with osteosarcoma achieved a partial response. On the other hand, 2 patients experienced grade 3 toxicities that required surgical treatment. CONCLUSION: RAS originates from various types of diseases that are treated by radiotherapy and shows diverse pathological features. Complete resection achieves a good prognosis. CIRT can be an effective and feasible option for unresectable RAS.

DOI： 10.1159/000521504

Activating HRAS mutation in a case of inverted ductal papilloma of the salivary gland. International journal

Fumio Ide, Yumi Ito, Kentaro Kikuchi, Kazuhito Satomura, Ikuko Ogawa, Hidetaka Yamamoto

Pathology international 71 ( 12 ) 844 - 848 2021.12

Language：English

Inverted ductal papilloma (IDP) is one of the least common benign papillary/cystic neoplasms of the salivary duct system, being characterized histologically by florid hyperplasia of duct-type epithelial cells into a cystic lumen near the orifice with occasional endophytic growth of the surface squamous epithelium along the terminus of the affected excretory duct. Given its rarity, the exact etiology of IDP remains to be defined. We herein present the first evidence of oncogenic HRAS mutation in a case of oral IDP. This finding, together with the frequent and specific BRAF mutations in sialadenoma papilliferum reported in the recent literature, supports an active role of the MAP-kinase cascade in the pathogenesis of benign papillary neoplasms of terminal duct origin.

DOI： 10.1111/pin.13166

Prognostic implication of desmoplastic stroma in synovial sarcoma: A histological review. International journal

Yu Toda, Yuichi Yamada, Kenichi Kohashi, Shin Ishihara, Yoshihiro Ito, Yosuke Susuki, Kengo Kawaguchi, Izumi Kinoshita, Daisuke Kiyozawa, Taro Mori, Yusuke Kuboyama, Yuki Tateishi, Hidetaka Yamamoto, Toshifumi Fujiwara, Nokitaka Setsu, Makoto Endo, Yoshihiro Matsumoto, Yasuharu Nakashima, Masaaki Mawatari, Yoshinao Oda

Pathology, research and practice 228 153668 - 153668 2021.12

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

Synovial sarcoma (SS) is a malignant soft tissue neoplasm harboring SS18-SSX fusion gene and is histologically characterized by spindle cells and epithelial components. Some investigations have demonstrated that desmoplastic reaction (DR) is an independent prognostic factor of cancers. However, it remains unknown whether DR is of predictive value for the prognosis of synovial sarcoma patients. Here, we reviewed the clinical and histological findings of 88 patients with SS. We defined DR as hyalinized collagenous structures and classified the degree of DR as follows: none, mild, moderate, and severe. Overall, 23 SS cases (24%) showed moderate or severe DR histologically. Statistically, the cases with moderate or severe degree of DR showed poorer prognosis than those with no or mild DR (local recurrence: P = 0.0059, distant metastasis: P = 0.0002, tumor death: P = 0.0382). The findings of the study suggest that the DR of synovial sarcoma could be an important prognostic factor.

DOI： 10.1016/j.prp.2021.153668

Alveolar soft part sarcoma of the orbit: A case report. International journal

Takeshi Oda, Kazufumi Kikuchi, Osamu Togao, Shingo Baba, Masahiro Mizoguchi, Mika Tanabe, Mamoru Ito, Hidetaka Yamamoto, Kousei Ishigami, Akio Hiwatashi

Radiology case reports 16 ( 12 ) 3766 - 3771 2021.12

Language：English

Alveolar soft part sarcoma is a rare soft tissue neoplasm that accounts for approximately 1% of all sarcomas and is usually identified in the extremities in adults. The occurrence of alveolar soft part sarcoma in the orbit is extremely rare, estimated at approximately 5% - 15% among all cases of alveolar soft part sarcoma . Here, we present a case of 29-year-old woman with orbital alveolar soft part sarcoma. We describe the magnetic resonance and F-18 2-fluoro-2-deoxy-D-glucose-position emission tomography/computed tomography findings of this case. This young woman had a spindle-shaped mass. A higher signal compared to the extraocular muscle on T1-weighted images, numerous flow voids on T2-weighted images, and intense enhancement could be key findings of this disease.

DOI： 10.1016/j.radcr.2021.09.005

Pathological review of cardiac amyloidosis using autopsy cases in a single Japanese institution. International journal

Yuki Tateishi, Yuichi Yamada, Masato Katsuki, Takuya Nagata, Hidetaka Yamamoto, Kenichi Kohashi, Yutaka Koga, Mikiko Hashisako, Daisuke Kiyozawa, Taro Mori, Yusuke Kuboyama, Ayumi Kakinokizono, Yoshiko Miyazaki, Aina Yamaguchi, Hiroyuki Tsutsui, Toshiharu Ninomiya, Hironobu Naiki, Yoshinao Oda

Pathology, research and practice 227 153635 - 153635 2021.11

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

AIM: Amyloidosis is a systemic or localized disease of protein deposition characterized by amorphous eosinophilic morphology and positivity of Congo Red staining. The typing of amyloidosis is becoming increasingly important because therapeutic agents for each amyloidosis type have been developed. Herein, the authors review the autopsy cases at an institution to reveal the putative Japanese characteristics of each amyloidosis type and evaluate the clinicopathological significance of each type. MATERIALS AND METHODS: A total of 131 autopsy cases of systemic and localized amyloidosis were retrieved for classification by immunohistochemistry. Immunohistochemistry for transthyretin, amyloid A (AA), immunoglobulin light-chain kappa and lambda, and β2-microglobulin was performed for all cases. RESULTS: The 131 amyloidosis cases were classified as follows: 71 cases (54.2%) of transthyretin amyloidosis, 32 cases (24.4%) of AA amyloidosis, 8 cases (6.1%) of light-chain amyloidosis, and 5 cases (3.8%) of β2-microglobulin amyloidosis, along with 15 equivocal cases (11.5%). All cases showed myocardial involvement of amyloidosis. Histopathologically, the transthyretin type was significantly associated with the interstitial and nodular patterns, and with the absence of the perivascular and endocardial patterns. The AA type was significantly associated with the perivascular and endocardial patterns, and with the absence of the nodular pattern. CONCLUSION: The authors revealed the putative characteristics of cardiac amyloidosis in Japan by using autopsy cases. About 90% of amyloidosis cases were successfully classified using only commercially available antibodies.

DOI： 10.1016/j.prp.2021.153635

Carcinoma showing thymus-like differentiation (CASTLE) of the salivary gland: Report of 2 cases of a hitherto under-recognized extrathyroid counterpart. International journal

Hidetaka Yamamoto, Kimihide Kusafuka, Yui Nozaki, Tomohiro Iwasaki, Miwako Nogami, Takahiro Hongo, Ryuji Yasumatsu, Yoshinao Oda

Pathology, research and practice 227 153646 - 153646 2021.11

Language：English

Carcinoma showing thymus-like differentiation (CASTLE) outside the thyroid gland is extremely rare. Here we report two cases of CASTLE of the major salivary gland. The tumors occurred in the parotid gland of a 31-year-old female (Case 1) and in the submandibular gland of a 40-year-old female (Case 2). Both tumors showed a lobulated growth pattern, and were histologically composed of a nested or sheet-like proliferation of carcinoma cells with round- to oval-shaped nuclei, distinct nucleoli and pale eosinophilic cytoplasm, accompanied by various degrees of lymphocytic infiltration. Immunohistochemical staining revealed that the tumors were positive for pan-cytokeratin, p40, CD5, CD117 and bcl-2. In addition, PD-L1 expression was seen in 10-90% of tumor cells. After the initial surgery, Case 1 remained tumor-free for 20 months, while Case 2 suffered lymph node recurrence at 4 months, followed by lung metastasis, which was treated with chemoradiotherapy and anti-PD-1 immune checkpoint inhibitor, resulting in a partial response. The present findings indicate that an extrathyroid counterpart of CASTLE can occur as a primary salivary gland neoplasm. Salivary CASTLEs seem to show a wide range of biological behavior, and long-term follow-up may be needed. Immune checkpoint inhibitor targeting PD-1 might become a promising treatment option in patients with CASTLE; however, further study with a larger number of cases is necessary to establish the optimal therapeutic strategy and prognostic factors for this rare cancer.

DOI： 10.1016/j.prp.2021.153646

Evaluation of MR imaging findings differentiating parotid basal cell adenomas from other parotid tumors. International journal

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

European journal of radiology 144 109980 - 109980 2021.11

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

PURPOSE: To evaluate the usefulness of magnetic resonance imaging (MRI) to differentiate basal cell adenomas (BCAs) from other parotid tumors. METHOD: A total of 136 patients with histologically proven parotid gland tumors (13 BCAs, 66 pleomorphic adenomas [PAs], 30 Warthin tumors [WTs], and 27 parotid cancers [PCs]) who underwent a cervical MRI study between December 2011 and March 2019 were retrospectively enrolled. The MRI findings of the tumors were evaluated by two board-certified radiologists. RESULTS: All 13 of the BCAs showed smooth margins, while 19 of the 27 PCs showed irregular margins (p < 0.0001). Eleven BCAs had some cystic components, and five were cyst-dominant. The BCAs had significantly more cystic components than the PAs (p = 0.0077). The mean apparent diffusion coefficient (ADC) value of the BCAs was 1.21 ± 0.20 × 10-3 mm2/sec, which was equivalent to that of the PCs (1.12 ± 0.25 × 10-3 mm2/sec, p = 0.76), significantly lower than that of the PAs (1.61 ± 0.32 × 10-3 mm2/sec, p < 0.0001), and significantly higher than that of the WTs (0.81 ± 0.19 × 10-3 mm2/sec, p = 0.0004). The plateau time-intensity curve (TIC) was the most common type for both BCAs and PCs, seen in 8 of 12 BCAs and 21 of 26 PCs, with no significant difference between these groups (p = 0.34). CONCLUSIONS: BCA should be considered a possibility when a parotid lesion has smooth margins with an entire capsule and includes a cystic component, even if the TIC and diffusion-weighted MR images suggest a malignant pattern.

DOI： 10.1016/j.ejrad.2021.109980

Does the Use of Peripheral Immune-Related Markers Indicate Whether to Administer Pazopanib, Trabectedin, or Eribulin to Advanced Soft Tissue Sarcoma Patients? International journal

Eijiro Shimada, Makoto Endo, Yoshihiro Matsumoto, Kenji Tsuchihashi, Mamoru Ito, Hitoshi Kusaba, Akira Nabeshima, Tomoya Nawata, Akira Maekawa, Tomoya Matsunobu, Nokitaka Setsu, Toshifumi Fujiwara, Keiichiro Iida, Makoto Nakagawa, Takeshi Hirose, Masaya Kanahori, Ryunosuke Oyama, Taichi Isobe, Hiroshi Ariyama, Kenichi Kohashi, Hidetaka Yamamoto, Yoshinao Oda, Yukihide Iwamoto, Koichi Akashi, Eishi Baba, Yasuharu Nakashima

Journal of clinical medicine 10 ( 21 ) 2021.10

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

Pazopanib, trabectedin, and eribulin are administered for the treatment of soft tissue sarcomas (STSs); however, there is little consensus on which agent should be preferentially used in a clinical setting. This study assessed whether peripheral immune-related markers served as a useful reference when selecting pazopanib, trabectedin, or eribulin. This study included 63 patients who were administered pazopanib, trabectedin, or eribulin for advanced STSs between March 2015 and December 2020. Patients were divided into three groups based on the first drug administered among these three drugs. Differences in overall survival (OS) or progression-free survival (PFS) among the three groups were analyzed. OS showed no significant differences among the drugs administered first. For patients with low neutrophil-to-lymphocyte ratio (NLR), the OS of patients administered pazopanib as the first choice was shorter than the others (hazard ratio [HR] = 9.53, 95% confidence interval [CI] = 1.94-18.13, p = 0.0018). In the low platelet-to-lymphocyte ratio (PLR) subgroup, the OS of the patients administered eribulin for the first choice was longer than that of the others (HR = 0.32, 95%CI = 0.10-0.98, p = 0.046). Therefore, NLR and PLR might be used as prognostic indicators to dictate whether STS patients receive pazopanib, trabectedin, or eribulin.

DOI： 10.3390/jcm10214972

A multi‐institutional study of salivary gland cytopathology: Application of the Milan System for Reporting Salivary Gland Cytopathology in Japan

Kayoko Higuchi, Makoto Urano, Jun Akiba, Miwako Nogami, Yukiya Hirata, Yoko Zukeran, Koki Moriyoshi, Yuichiro Tada, Mana Fukushima, Mariko Obayashi, Shinnichi Sakamoto, Kazuya Kuraoka, Kana Kira, Akihiko Kawahara, Taku Kato, Maki Tanigawa, Masato Nakaguro, Hidetaka Yamamoto, Toshitaka Nagao

Cancer Cytopathology 130 ( 1 ) 30 - 40 2021.9

生物学的製剤使用の患者におけるメトトレキサート関連リンパ腫の後方視的研究(Clinical outcome of methotrexate-associated lymphoproliferative disorders)

原田卓哉, 岩崎浩己, 牟田毅, 浦田慎吾, 坂本愛子, 河野健太郎, 高瀬謙, 宮村知也, 澤部琢哉, 麻奥英毅, 押領司健介, 藤崎智明, 森康雄, 吉本五一, 綾野雅宏, 三苫弘喜, 宮本敏浩, 新納宏昭, 山元英崇, 大城由美, 三好寛明, 大島孝一, 竹下盛重, 加藤光次, 赤司浩一

日本血液学会学術集会 83回 OS1 - 2 2021.9

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