Details of a Researcher - SUGITA Shintarou

Papers - SUGITA Shintarou

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Loss of Tapasin in Tumors Potentiates T-Cell Recognition and Anti-Tumor Effects of Immune Checkpoint Blockade.

Keigo Moniwa, Serina Tokita, Toshiyuki Sumi, Hiroshi Saijo, Shintaro Sugita, Kotomi Arioka, Yoshihiko Hirohashi, Hirofumi Chiba, Takayuki Kanaseki, Toshihiko Torigoe

Cancer science 2025.02 [International journal]

Tumors can evade host immune surveillance by compromising the intracellular antigen processing machinery (APM), such as beta 2 macroglobulin (β2m) or the transporter associated with antigen processing (TAP). Defects in the APM generally result in the downregulation of surface MHC class I (MHC-I) levels. Here, we show that the downregulation of a component of the peptide loading complex (PLC), tapasin, in tumors conversely induces CD8+ T-cell responses and inhibits tumor growth in vivo. Loss of tapasin enhanced the anti-tumor effects of immune checkpoint blockade (ICB) in mouse non-small cell lung and colon cancer models. In contrast to β2m-deficient tumors, the reduced levels of MHC-I in tapasin-deficient tumors were restored by IFN-γ treatment, allowing them to be recognized by CD8+ T cells. These results suggest the presence of a reactive CD8+ T-cell fraction and the ability of immune surveillance to eliminate tumor variants with impaired tapasin expression.

DOI PubMed

Case Report: Severe Immune-Related Adverse Event Under Pembrolizumab Therapy for Discoid Lupus Erythematosus-Related Squamous Cell Carcinoma.

Hidenori Amaike, Hiroyuki Nakamura, Koki Nakamura, Ken Nagahata, Kohei Horimoto, Junji Kato, Masatoshi Kanda, Shintaro Sugita, Hisashi Uhara, Hiroki Takahashi

International journal of rheumatic diseases 28 ( 2 ) e70108 2025.02 [International journal]

DOI PubMed

Ulcerative Colitis Preceding Asymptomatic Wilson’s Disease: A Case Report and Literature Review

Jun Kunizaki, Yuko Yoto, Yoshinobu Nagaoka, Akira Ishii, Tomoe Kazama, Kohei Wagatsuma, Noriyuki Akutsu, Aki Ishikawa, Toju Tanaka, Shintaro Sugita, Takeshi Tsugawa, Hiroshi Nakase

Gastro Hep Advances ( Elsevier BV ) 4 ( 1 ) 100548 - 100548 2025

DOI

Identification and phenotypic characterization of neoantigen-specific cytotoxic CD4+ T cells in endometrial cancer

Minami Fusagawa, Serina Tokita, Kenji Murata, Tasuku Mariya, Mina Umemoto, Shintaro Sugita, Kazuhiko Matsuo, Yoshihiko Hirohashi, Tsuyoshi Saito, Takayuki Kanaseki, Toshihiko Torigoe

Cancer Immunology Research ( American Association for Cancer Research (AACR) ) 2024.12

Abstract Tumor-reactive CD4+ T cells often accumulate in the tumor microenvironment (TME) in human cancer, but their functions and roles in antitumor responses remain elusive. Here, we investigated the immunopeptidome of HLA class II–positive (HLA-II+) endometrial cancer with an inflamed TME using a proteogenomic approach. We identified HLA-II neoantigens, one of which induced polyclonal CD4+ tumor-infiltrating lymphocyte (TIL) responses. We then experimentally demonstrated that neoantigen-specific CD4+ TILs lyse target cells in an HLA-II–dependent manner. Single cell transcriptomic analysis of the TME coupled with T-cell receptor (TCR) sequencing revealed the presence of CD4+ T-cell clusters characterized by CXCL13 expression. The CXCL13+ clusters contained two subclusters with distinct cytotoxic gene expression patterns. The identified neoantigen-specific CD4+ T cells were found exclusively in one of the CXCL13+ subclusters characterized by granzyme B and CCL5 expression. These results demonstrate the involvement of tumor-reactive CD4+ T cells with cytotoxic function in immune surveillance of endometrial cancer and reveal their transcriptomic signature.

DOI

Establishment and characterization of the novel myxofibrosarcoma cell line, SMU-MFS

Naoya Nakahashi, Makoto Emori, Kohichi Takada, Yasutaka Murahashi, Junya Shimizu, Kazuyuki Murase, Tomohide Tsukahara, Shintaro Sugita, Akira Takasawa, Kousuke Iba, Atsushi Teramoto, Makoto Osanai

Human Cell ( Springer Science and Business Media LLC ) 38 ( 1 ) 2024.12

DOI

Secondary Osteosarcoma After Carbon‐Ion Radiotherapy for Desmoid‐Type Fibromatosis: A Case Report

Mizuki Aketo, Makoto Emori, Kohichi Takada, Kazuyuki Murase, Yohei Arihara, Junya Shimizu, Yasutaka Murahashi, Masahiko Okamoto, Shintaro Sugita, Atsushi Teramoto

Cancer Reports ( Wiley ) 7 ( 11 ) 2024.11

ABSTRACT Background Radiotherapy is considered an alternative treatment for unresectable or pharmacologically resistant desmoid‐type fibromatosis. While it results in relatively good local control, the risk of secondary malignancy remains a concern. Case We present a case of secondary osteosarcoma after carbon‐ion radiation therapy (CIRT). A 31‐year‐old male patient presented with left thigh pain. The tumor was located between the left gluteus maximus and gluteus medius and extended to the vastus lateralis and biceps femoris. It was diagnosed as desmoid‐type fibromatosis after needle biopsy. The patient was treated with several medications, including a cyclooxygenase 2 inhibitor and tamoxifen; however, his left thigh pain did not improve. He was treated with CIRT 1 year after diagnosis (67.2 Gy [relative biological effectiveness] 16fr/4wks). He developed osteosarcoma of the left femur 8 years later. He underwent chemotherapy and tumor excision with disarticulation of the left hip. Pulmonary metastasis was detected 6 and 17 months after the definitive surgery and excised using metastasectomy. However, he died due to the recurrence of multiple pulmonary metastases 29 months after the definitive surgery. Conclusions In this case, we believe that the low radiation dose to the femur may have caused secondary malignancy.

DOI

Germline <scp>BRCA1</scp>‐Mutated Synchronous and Metachronous Pancreatic Acinar Cell Carcinoma With Long‐Term Survival

Tomohiro Kubo, Yuki Ikeda, Joji Muramatu, Kazuma Ishikawa, Makoto Yoshida, Kazuharu Kukita, Masafumi Imamura, Shintaro Sugita, Akihiro Sakurai, Kohichi Takada

Cancer Reports ( Wiley ) 7 ( 8 ) 2024.08

ABSTRACT Background Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic neoplasm. Recently, molecular analysis revealed that PACC shows a high frequency of the BRCA1/2 mutation and is likely to be considered a cancer associated with hereditary breast and ovarian cancer (HBOC). Hereditary cancers, including HBOC, are characterized by multifocal and/or metachronous tumors. However, no case reports exist of germline BRCA1‐mutated synchronous and metachronous PACC. Case A 58‐year‐old man was diagnosed with synchronous and metachronous PACC at the age of 56 and underwent two surgeries. Ten months after the second surgery, the patient developed multiple liver metastases. Gemcitabine plus nab‐paclitaxel therapy was administered as first‐line chemotherapy. After seven cycles, computed tomography examination revealed progressive disease (PD). Therefore, modified FOLFIRINOX (mFFX) was administered as second‐ line chemotherapy. After 19 cycles of mFFX, comprehensive cancer genomic profiling (CGP) identified a BRCA1 pathogenic variant that was confirmed to be germline origin. Accordingly, we treated the patient with olaparib; however, he was diagnosed with PD after 4 months. He subsequently died 5 years and 9 months after the initial surgery, and 3 years and 10 months after chemotherapy. Based on the genetic data of the patients, his family members received genetic counseling followed by cascade testing. Consequently, the same gBRCA1 pathogenic variant was detected in the son and his surveillance for HBOC‐related cancers was initiated. Conclusion We diagnosed a 58‐year‐old man with a synchronous and metachronous PACC with germline BRCA1 pathogenic variant. Considering that PACC is likely to have BRCA1/2 mutations responsible for HBOC, we need to be aware of the possible presence of multifocal and/or metachronous tumors in patients with PACC. Additionally, patients with PACC should undergo genetic examinations, which would be beneficial in determining treatment strategies and health care for blood relatives.

DOI

LMNA::NTRK1 Fusion-positive Leiomyosarcoma: Discrepancy between DNA-based Comprehensive Genomic Profiling and RNA Sequencing.

Norito Suzuki, Masashi Idogawa, Makoto Emori, Kazuyuki Murase, Yohei Arihara, Hajime Nakamura, Makoto Usami, Tomohiro Kubo, Ichiro Kinoshita, Shintaro Sugita, Takashi Tokino, Tadashi Hasegawa, Akihiro Sakurai, Kohichi Takada

Internal medicine (Tokyo, Japan) 63 ( 15 ) 2215 - 2219 2024.08 [Domestic journal]

A 26-year-old man presented with a tumor in the left soleus muscle. The tumor was diagnosed as a locally advanced leiomyosarcoma. The patient was treated with irradiation followed by wide resection. One year after surgery, the patient presented with multiple lung metastases. Despite aggressive sequential chemotherapy, systemic metastatic tumors continued to develop. To explore therapeutic options for the patient, we performed DNA-based CGP with FoundationOne® CDx (F1). F1 identified an out-of-strand rearrangement of the NOS1AP::NTRK1 gene, which has not been previously reported. In contrast, RNA sequencing revealed an in-frame LMNA::NTRK1 gene, which is an oncogenic fusion gene.

DOI PubMed

Unique endoscopic features of primary biliary diffuse large B‐cell lymphoma: A case report with literature review (with video)

Tomoya Nakamura, Yoshiharu Masaki, Naohiro Kameyama, Yujiro Kawakami, Keisuke Ishigami, Yumemi Takada, Shuji Satoh, Taro Sugawara, Shintaro Sugita, Hiroshi Nakase

DEN Open ( Wiley ) 5 ( 1 ) 2024.07

Abstract A 67‐year‐old man visited our hospital complaining of dark‐colored urine and upper abdominal pain. Magnetic resonance cholangiopancreatography showed stricture of the distal bile duct, and contrast‐enhanced computed tomography showed irregular thickening of the distal bile duct wall. However, no enlarged lymph nodes, pancreatic tumors, or other neoplastic lesions were apparent around the bile duct. Endoscopic ultrasonography and intraductal ultrasonography showed irregular thickening of the inner hypoechoic layer without the disappearance of the innermost thin hyperechoic layer. On the basis of these findings, we considered that the bile duct lesion was of non‐epithelial origin. Thus, we repeatedly performed bile duct biopsies from the same site under fluoroscopy to obtain a sample of the submucosal tissue. The pathological diagnosis was diffuse large B‐cell lymphoma, and the patient received systemic chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). After six courses of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, positron emission tomography‐computed tomography showed the disappearance of 18‐fluorodeoxyglucose uptake in the bile duct and endoscopic retrograde cholangiography showed improvement of the bile duct stricture. Endoscopic findings and repeated biopsies were useful in making the diagnosis of primary biliary diffuse large B‐cell lymphoma.

DOI

Marked Response to Nivolumab by a Patient With <scp>SMARCA4</scp>‐Deficient Undifferentiated Urothelial Carcinoma Showing High <scp>PD</scp>‐<scp>L1</scp> Expression: A Case Report

Yohei Arihara, Ginji Omori, Ko Kobayashi, Shintaro Sugita, Kazuyuki Murase, Tomohiro Kubo, Masashi Idogawa, Tadashi Hasegawa, Kohichi Takada

Cancer Reports ( Wiley ) 7 ( 6 ) 2024.06

ABSTRACT Background SMARCA4 is a component gene of the SWI/SNF (SWItch/Sucrose NonFermentable) chromatin remodeling complex; undifferentiated tumors associated with its functional deletion have been described in several organs. However, no established treatment for these tumors currently exists. Case In this study, we report a case of a SMARCA4‐deficient undifferentiated urothelial carcinoma with high PD‐L1 expression that was effectively treated with nivolumab after early relapse following treatment for non‐invasive bladder cancer. The histological morphology of the rhabdoid‐like undifferentiated tumor of unknown primary led us to suspect a SWI/SNF‐deficient tumor, and subsequent immunostaining led to the diagnosis of a SMARCA4‐deficient undifferentiated tumor. This effort also led to the identification of the developmental origin of this SMARCA4‐deficient undifferentiated tumor as a non‐invasive bladder cancer. We also carried out a detailed immune phenotypic assay on peripheral T cells. In brief, a phenotypic change of CD8+T cells from naive to terminally differentiated effector memory cells was observed. Conclusion Regardless of the organ of cancer origin or cancer type, SWI/SNF‐deficient tumors should be suspected in undifferentiated and dedifferentiated tumors, and immune checkpoint inhibitors may be considered as a promising treatment option for this type of tumor. The pathogenesis of SMARCA4‐deficient anaplastic tumors awaits further elucidation for therapeutic development.

DOI

Crizotinib therapy for congenital embryonal rhabdomyosarcoma associated with an ATIC–ALK gene fusion

Yusuke Akane, Masaki Yamamoto, Akira Takebayashi, Ryo Hamada, Keita Igarashi, Makoto Emori, Shintaro Sugita, Kohichi Takada, Tadashi Hasegawa, Takeshi Tsugawa

Pediatric Blood & Cancer ( Wiley ) 2024.06

DOI

Peroral cholangioscopy-guided biopsy with novel biopsy forceps in comprehensive cancer genomic profiling for cystic duct carcinoma

Yujiro Kawakami, Yoshiharu Masaki, Keisuke Ishigami, Takehiro Hirano, Ayako Murota, Shintaro Sugita, Hiroshi Nakase

Endoscopy ( Georg Thieme Verlag KG ) 56 ( S 01 ) E414 - E415 2024.05

DOI

Prediction of Mismatch Repair Status in Endometrial Cancer from Histological Slide Images Using Various Deep Learning-Based Algorithms.

Mina Umemoto, Tasuku Mariya, Yuta Nambu, Mai Nagata, Toshihiro Horimai, Shintaro Sugita, Takayuki Kanaseki, Yuka Takenaka, Shota Shinkai, Motoki Matsuura, Masahiro Iwasaki, Yoshihiko Hirohashi, Tadashi Hasegawa, Toshihiko Torigoe, Yuichi Fujino, Tsuyoshi Saito

Cancers 16 ( 10 ) 2024.05 [International journal]

The application of deep learning algorithms to predict the molecular profiles of various cancers from digital images of hematoxylin and eosin (H&E)-stained slides has been reported in recent years, mainly for gastric and colon cancers. In this study, we investigated the potential use of H&E-stained endometrial cancer slide images to predict the associated mismatch repair (MMR) status. H&E-stained slide images were collected from 127 cases of the primary lesion of endometrial cancer. After digitization using a Nanozoomer virtual slide scanner (Hamamatsu Photonics), we segmented the scanned images into 5397 tiles of 512 × 512 pixels. The MMR proteins (PMS2, MSH6) were immunohistochemically stained, classified into MMR proficient/deficient, and annotated for each case and tile. We trained several neural networks, including convolutional and attention-based networks, using tiles annotated with the MMR status. Among the tested networks, ResNet50 exhibited the highest area under the receiver operating characteristic curve (AUROC) of 0.91 for predicting the MMR status. The constructed prediction algorithm may be applicable to other molecular profiles and useful for pre-screening before implementing other, more costly genetic profiling tests.

DOI PubMed

Prognostic evaluation of the Ki-67 labeling system in histological grading of non-small round cell sarcoma: a supplementary analysis of a randomized controlled trial, JCOG1306

Shintaro Sugita, Kazuhiro Tanaka, Yoshinao Oda, Takayuki Nojima, Naomi Konishi, Ryunosuke Machida, Ryosuke Kita, Haruhiko Fukuda, Toshifumi Ozaki, Tadashi Hasegawa

Japanese Journal of Clinical Oncology ( Oxford University Press (OUP) ) 2024.02

Authorship： Lead author

Abstract Background Soft tissue sarcoma (STS) has various histological types and is rare, making it difficult to evaluate the malignancy of each histological type. Thus, comprehensive histological grading is most important in the pathological examination of STS. The Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system is most commonly used in daily pathological analysis of STS. Among the FNCLCC grading system parameters, mitotic count is a key morphological parameter reflecting the proliferative activity of tumor cells, although its reproducibility may be lacking. Here, we compared the prognostic utility of the conventional and modified FNCLCC grading systems in JCOG1306. Methods We analyzed 140 patients with non-small round cell sarcoma. We performed Ki-67 immunostaining using open biopsy specimens before preoperative chemotherapy in all patients. We assessed histological grade in individual cases by conventional FNCLCC grading (tumor differentiation, mitotic count, and necrosis) and modified FNCLCC grading using the Ki-67 labeling index instead of mitotic count. We conducted univariable and multivariable Cox regression analyses to investigate the influence of grade on overall survival. Results In univariable analysis, prognosis was worse for patients with conventional FNCLCC Grade 3 tumors compared with Grade 1 or 2 tumors (hazard ratio [HR] 4.21, 95% confidence interval [CI] 1.47–12.05, P = 0.008). Moreover, prognosis was worse in patients with modified FNCLCC Grade 3 tumors compared with Grade 1 or 2 tumors (HR 4.90, 95% CI 1.64–14.65, P = 0.004). In multivariable analysis including both conventional and modified FNCLCC grading, the modified grading more strongly affected overall survival (HR 6.70, 95% CI 1.58–28.40, P = 0.010). Conclusions The modified FNCLCC grading system was superior to the conventional system in predicting the prognosis of patients with non-small round cell sarcoma according to this supplementary analysis of data from the randomized controlled trial JCOG1306.

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Gap junction beta‐4 accelerates cell cycle progression and metastasis through MET–AKT activation in pancreatic cancer

Joji Muramatsu, Yohei Arihara, Makoto Yoshida, Tomohiro Kubo, Hajime Nakamura, Kazuma Ishikawa, Hiromi Fujita, Shintaro Sugita, Takumi Konno, Takashi Kojima, Yutaka Kawano, Masayoshi Kobune, Kohichi Takada

Cancer Science ( Wiley ) 2024.02

Abstract Despite continuing advances in the development of effective new therapies, including immunotherapies, the prognosis of pancreatic cancer remains extremely poor. Gap junction proteins have become attractive targets for potential cancer therapy. However, the role of gap junction beta‐4 (GJB4) protein remains unexplored in pancreatic cancer. Through bioinformatic analyses we discovered pancreatic cancer tissues showed higher levels of GJB4 transcripts compared to normal pancreatic tissues and this had a negative effect on overall survival in patients that had pancreatic cancer. The high expression of nuclear GJB4 was identified as a negative prognostic factor in such patients. Knockdown of GJB4 in cultured pancreatic cancer cells resulted in G₀/G₁ arrest followed by decreased cell proliferation and suppression of metastatic potential. The overexpression of GJB4 accelerated cell proliferation, migration, and invasion in a SUIT‐2 cell line, whereas MET inhibitor canceled the acceleration. GJB4 suppression with siRNA significantly inhibited tumor growth in a mouse xenograft model. Mechanistically, suppression of GJB4 inhibited MET–AKT activities. Such data suggest that targeting the GJB4–MET axis could represent a promising new therapeutic strategy for pancreatic cancer.

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Acanthopanax senticosus ameliorates steatohepatitis through HNF4 alpha pathway activation in mice

Yutaka Kawano, Maki Tanaka, Yasushi Satoh, Shigekazu Sugino, Jun Suzuki, Masaki Fujishima, Eri Okumura, Hideo Takekoshi, Osamu Uehara, Shintaro Sugita, Yoshihiro Abiko, Tetsu Tomonari, Hironori Tanaka, Hidekatsu Takeda, Tetsuji Takayama

Scientific Reports ( Springer Science and Business Media LLC ) 14 ( 1 ) 2024.01

Abstract Non-alcoholic fatty liver disease is a common liver disease worldwide, and is associated with dysregulation of lipid metabolism, leading to inflammation and fibrosis. Acanthopanax senticosus Harms (ASH) is widely used in traditional medicine as an adaptogen food. We examined the effect of ASH on steatohepatitis using a high-fat diet mouse model. Mice were fed a choline-deficient, l-amino acid-defined, high-fat diet with ASH extract (ASHE). After 6 weeks, liver RNA transcriptome sequencing (RNA-Seq) was performed, followed by Ingenuity Pathway Analysis (IPA). Our findings revealed that mice fed a high-fat diet with 5% ASHE exhibited significantly reduced liver steatosis. These mice also demonstrated alleviated inflammation and reduced fibrosis in the liver. IPA of RNA-Seq indicated that hepatocyte nuclear factor 4 alpha (HNF4 alpha), a transcription factor, was the activated upstream regulator (P-value 0.00155, z score = 2.413) in the liver of ASHE-fed mice. Adenosine triphosphate binding cassette transporter 8 and carboxylesterase 2, downstream targets of HNF4 alpha pathway, were upregulated. Finally, ASHE-treated HepG2 cells exposed to palmitate exhibited significantly decreased lipid droplet contents. Our study provides that ASHE can activate HNF4 alpha pathway and promote fat secretion from hepatocytes, thereby serving as a prophylactic treatment for steatohepatitis in mice.

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High-grade B-cell lymphoma, not otherwise specified, presenting as primary peritoneal lymphomatosis and successfully treated with dose-adjusted EPOCH-R

Akihito Fujimi, Yasuhiro Nagamachi, Naofumi Yamauchi, Naoki Onoyama, Naotaka Hayasaka, Teppei Matsuno, Kazuhiko Koike, Yoshiro Goto, Kohji Ihara, Junji Kato, Takuji Nishisato, Hiroshi Kawase, Tomoyuki Yano, Takayuki Kanaseki, Shintaro Sugita, Masayoshi Kobune

Journal of Clinical and Experimental Hematopathology ( Japanese Society for Lymphoreticular Tissue Research ) 2024

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Identification of cancer driver mutations in liquid-based cytology samples for the screening of endometrial diseases

Motoki Matsuura, Kiyoko Takane, Kiyoshi Yamaguchi, Tsuneo Ikenoue, Seira Hatakeyama, Shoko Kurokawa, Masato Tamate, Taishi Akimoto, Masahiro Iwasaki, Shintaro Sugita, Tadashi Hasegawa, Yasunori Ota, Tsuyoshi Saito, Yoichi Furukawa

BJC Reports ( Springer Science and Business Media LLC ) 1 ( 1 ) 2023.11

Abstract Background Endometrial cancer (EC) is one of the leading causes of cancer death among women and early detection is crucial for its successful treatment. We previously showed that cytological examination combined with genetic analysis using liquid-based cytology (LBC) samples improved the diagnostic sensitivity of EC. Methods Among 218 individuals who underwent endometrial screening by LBC, 208 samples were analysed by cancer-panel sequencing. Excluding 13 samples with low sequence coverage, we further analysed 195 samples. Results Among the 195 women analysed, 39 and 15 were eventually shown to suffer from malignant endometrial and non-endometrial neoplasms, respectively. Driver mutation(s) were found in nine of the 15 cytology-negative patients with endometrial malignancy, corroborating that combination of cytological and genetic analyses should increase the sensitivity of the diagnosis of malignant endometrial neoplasms. Importantly, driver alterations were found in 32 of 125 women without malignant or premalignant diseases, which raises caution for the interpretation of genetic alterations detected in the endometrial samples. Comparison between the driver mutations in the 32 subjects and those in the 29 endometrial malignancies unveiled that the number of mutations and mutations in PTEN, CTNNB1, and TP53 may be applied for the assessment and prediction of development of EC. Conclusions The genetic analysis combined with liquid-based cytology is useful to improve the diagnostic sensitivity of endometrial neoplasms. However, caution must be taken when cancer-associated mutation(s) are detected in the genetic analysis. Further investigation may clarify the risk of malignant endometrial neoplasms in women with driver mutation(s).

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A case of IgG4-related cholecystitis diagnosed by transpapillary gallbladder biopsy using a novel device delivery system

Yujiro Kawakami, Naohiro Kameyama, Yosuke Hirobe, Yoshiharu Masaki, Ayako Murota, Shintaro Sugita, Hiroshi Nakase

Endoscopy ( Georg Thieme Verlag KG ) 55 ( S 01 ) E1108 - E1110 2023.10

DOI

Four cases of gnathostomiasis due to the ingestion of raw Salangichthys microdon

Takahiko Abe, Tokimasa Hida, Takafumi Kamiya, Kanako Ebata, Shintaro Sugita, Rie Kaneko, Mio Tanaka, Haruhiko Maruyama, Akira Suzuki, Hisashi Uhara

The Journal of Dermatology ( Wiley ) 2023.10

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Coefficient of variation of T2-weighted MRI may predict the prognosis of malignant peripheral nerve sheath tumor

Makoto Emori, Hiroyuki Tsuchie, Hiroyuki Takashima, Atsushi Teramoto, Yasutaka Murahashi, Yoshinori Imura, Hidetatsu Outani, Sho Nakai, Satoshi Takenaka, Ryosuke Hirota, Naoya Nakahashi, Junya Shimizu, Kazuyuki Murase, Akira Takasawa, Hiroyuki Nagasawa, Shintaro Sugita, Kohichi Takada, Tadashi Hasegawa, Seiji Okada, Naohisa Miyakoshi, Toshihiko Yamashita

Skeletal Radiology ( Springer Science and Business Media LLC ) 2023.09

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Systemic mastocytosis observed by image-enhanced endoscopy

Ryota Seto, Shinji Yoshii, Tomoe Kazama, Tsukasa Yamakawa, Shintaro Sugita, Hiro-o Yamano, Hiroshi Nakase

American Journal of Gastroenterology ( Ovid Technologies (Wolters Kluwer Health) ) 2023.09

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Pemphigus vulgaris as an immune-related adverse event in recurrent metastatic esophageal squamous cell carcinoma treated with ipilimumab plus nivolumab: a case report and literature review

Hajime Nakamura, Aika Shionoya, Yohei Arihara, Naotaka Hayasaka, Tomohiro Kubo, Makoto Usami, Shintaro Sugita, Hisashi Uhara, Kohichi Takada

Frontiers in Immunology ( Frontiers Media SA ) 14 2023.09

Ipilimumab plus nivolumab therapy is approved for patients with unresectable advanced esophageal squamous cell carcinoma (ESCC). Although a combination of immune checkpoint inhibitors (ICIs), compared to conventional chemotherapy, can improve overall survival in patients with advanced ESCC, this increases the incidence of immune-related adverse events (irAEs). Here, we describe an ESCC case that developed pemphigus vulgaris (PV), an extremely rare cutaneous irAE, during ipilimumab plus nivolumab treatment. The patient achieved a partial response to treatment. The PV was successfully managed after the cessation of ipilimumab and the use of a topical steroid. We should thus re-treat ESCC with nivolumab monotherapy. In the era of ICIs as standard cancer therapeutics, diagnostic criteria for blistering diseases need to be established to properly manage patients with cutaneous irAEs.

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Establishment and characterization of a novel dedifferentiated chondrosarcoma cell line, SMU-DDCS, harboring an IDH1 mutation

Makoto Emori, Naoya Nakahashi, Akira Takasawa, Kenji Murata, Yasutaka Murahashi, Junya Shimizu, Tomohide Tsukahara, Shintaro Sugita, Kohichi Takada, Tadashi Hasegawa, Makoto Osanai, Kosuke Iba

Human Cell ( Springer Science and Business Media LLC ) 2023.07

DOI

A rare case report of diverticulum of the buccal mucosa

Kazushige Koike, Hinako Mori, Kazuhiro Ogi, Makiya Jin, Satoshi Ohwada, Takahiro Iwamoto, Shintaro Sugita, Tadashi Hasegawa, Akihiro Miyazaki

Clinical Case Reports ( Wiley ) 11 ( 7 ) 2023.07

DOI

Ischemia-induced intestinal de-epithelization and consequent cholangitis lenta after usage of extracorporeal membrane oxygenation in COVID-19 patients: an autopsy series

Sae Hatanaka, Yuki Yamada, Terufumi Kubo, Kazufumi Magara, Yusuke Ono, Shintaro Sugita, Tomohide Tsukahara, Daisuke Kyuno, Michiko Hosaka, Kenta Sasaki, Yoshihiko Hirohashi, Tsukasa Yamakawa, Keisuke Harada, Naofumi Bunya, Eichi Narimatsu, Hiroshi Nakase, Tadashi Hasegawa, Makoto Osanai, Toshihiko Torigoe

Oxford Medical Case Reports ( Oxford University Press (OUP) ) 2023 ( 4 ) 2023.04

Abstract Since its discovery in late 2019, severe acute respiratory syndrome coronavirus 2 has spread around the world, causing millions of deaths due to coronavirus disease 2019 (COVID-19). Numerous clinical and post-mortem investigations of COVID-19 cases have found myriad clinical and pathological manifestations of the disease. In this report, we present three autopsy cases in which, despite weaning from extracorporeal membrane oxygenation (ECMO), extensive intestinal epithelial shedding, probably due to ischemia, was followed by massive watery diarrhea and the spread of infection via the portal vein due to bacterial translocation, which resulted in cholangitis lenta. Thrombophilia was attributed to ECMO usage and COVID-19-related vascular endothelial damage. These cases provide instructive findings showing that the loss of the intestinal barrier may be the underlying cause of severe watery diarrhea and liver failure in COVID-19 patients, especially with ECMO usage.

DOI

Usefulness of cell block examination for the cytological diagnosis of thoracic <scp>SMARCA4</scp> ‐deficient undifferentiated tumor: A case report

Atsushi Minoshima, Shintaro Sugita, Keiko Segawa, Tomoyuki Aoyama, Mikako Ito, Fuminori Daimon, Tomoko Takenami, Tomomi Kido, Jun Moriya, Hirotaka Nishikiori, Tadashi Hasegawa

Diagnostic Cytopathology ( Wiley ) 2023.02

Authorship： Corresponding author

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Achievement of a durable response with eribulin for relapsed cardiac metastasis of uterine leiomyosarcoma after surgery: a case report and literature review

Makoto Usami, Kohichi Takada, Hajime Nakamura, Kazuyuki Murase, Yohei Arihara, Naotaka Hayasaka, Tomohiro Kubo, Koji Miyanishi, Junji Kato, Makoto Emori, Shintaro Sugita

Annals of Palliative Medicine ( AME Publishing Company ) 12 ( 1 ) 205 - 211 2023.01

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A Case of Atypical Pseudo-Meigs' Syndrome without Pleural Effusion due to Ovarian Metastasis from Sigmoid Colon Cancer

Ginji Omori, Yohei Arihara, Tomoyuki Abe, Kohichi Takada, Norito Suzuki, Ryo Shibuya, Yuki Ikeda, Michiko Yamada, Michihiro Ono, Miri Fujita, Shintaro Sugita, Masahiro Maeda

Internal Medicine ( Japanese Society of Internal Medicine ) 2023

DOI

A Case of Immunoglobulin G4-Related Gastrointestinal Disease Diagnosed From Persistent Diarrhea and Abdominal Pain.

Takehiro Hirano, Yujiro Kawakami, Sayaka Nakabayashi, Kohei Wagatsuma, Keisuke Ishigami, Yoshiharu Masaki, Ayako Murota, Masatoshi Kanda, Shintaro Sugita, Kenji Notohara, Hiroshi Nakase

Gastro hep advances 2 ( 8 ) 1089 - 1092 2023 [International journal]

Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by the infiltration of IgG4-positive plasma cells and fibrosis in organs throughout the body. IgG4-RD involvement in the gastrointestinal (GI) tract (IgG4-related GI disease; IgG4-GID) is rare, and the disease concept remains unclear. Generally, IgG4-GID has been reported with morphological changes, including ulcers, strictures, and submucosal tumors. Here, we report a case of IgG4-GID with persistent diarrhea and abdominal pain in which typical endoscopic findings were absent. This case suggests the unidentified clinical features of IgG4-GID.

DOI PubMed

Diagnostic utility of CSF1 immunohistochemistry in tenosynovial giant cell tumor for differentiating from giant cell-rich tumors and tumor-like lesions of bone and soft tissue

Shintaro Sugita, Tomoko Takenami, Tomomi Kido, Tomoyuki Aoyama, Michiko Hosaka, Keiko Segawa, Taro Sugawara, Hiromi Fujita, Junya Shimizu, Yasutaka Murahashi, Makoto Emori, Tadashi Hasegawa

Diagnostic Pathology ( Springer Science and Business Media LLC ) 17 ( 1 ) 2022.11

Authorship： Lead author

Abstract Background Tenosynovial giant cell tumor (TSGCT) is a benign fibrohistiocytic tumor that affects the synovium of joints, bursa, and tendon sheaths and is categorized into localized TSGCT (LTSGCT) and diffuse TSGCT (DTSGCT). LTSGCT and DTSGCT are characterized by recurrent fusions involving the colony-stimulating factor 1 (CSF1) gene and its translocation partner collagen type VI alpha 3 chain. The fusion gene induces intratumoral overexpression of CSF1 mRNA and CSF1 protein. CSF1 expression is a characteristic finding of TSGCT and detection of CSF1 mRNA and CSF1 protein may be useful for the pathological diagnosis. Although there have been no effective anti-CSF1 antibodies to date, in situ hybridization (ISH) for CSF1 mRNA has been performed to detect CSF1 expression in TSGCT. We performed CSF1 immunohistochemistry (IHC) using anti-CSF1 antibody (clone 2D10) in cases of TSGCT, giant cell-rich tumor (GCRT), and GCRT-like lesion and verified its utility for the pathological diagnosis of TSGCT. Methods We performed CSF1 IHC in 110 cases including 44 LTSGCTs, 20 DTSGCTs, 1 malignant TSGCT (MTSGCT), 10 giant cell tumors of bone, 2 giant cell reparative granulomas, 3 aneurysmal bone cysts, 10 undifferentiated pleomorphic sarcomas, 10 leiomyosarcomas, and 10 myxofibrosarcomas. We performed fluorescence ISH (FISH) for CSF1 rearrangement to confirm CSF1 expression on IHC in TSGCTs. We considered the specimens to have CSF1 rearrangement if a split signal was observed in greater than 2% of the tumor cells. Results Overall, 50 of 65 TSGCT cases, including 35 of the 44 LTSGCTs and 15 of the 20 DTSGCTs, showed distinct scattered expression of CSF1 in the majority of mononuclear tumor cells. MTSGCT showed no CSF1 expression. Non-TSGCT cases were negative for CSF1. FISH revealed CSF1 rearrangement in 6 of 7 CSF1-positive cases on IHC. On the other hand, FISH detected no CSF1 rearrangement in all CSF1-negative cases on IHC. Thus, the results of IHC corresponded to those of FISH. Conclusion We revealed characteristic CSF1 expression on IHC in cases of TSGCT, whereas the cases of non-TSGCT exhibited no CSF1 expression. CSF1 IHC may be useful for differentiating TSGCTs from histologically mimicking GCRTs and GCRT-like lesions.

DOI

Usefulness of SynCAM3 and cyclin D1 immunohistochemistry in distinguishing superficial CD34-positive fibroblastic tumor from its histological mimics.

Sugita S, Takenami T, Kido T, Aoyama T, Hosaka M, Segawa K, Sugawara T, Fujita H, Murahashi Y, Emori M, Tsuyuki A, Hasegawa T

Med Mol Morphol 2022.11

Authorship： Lead author

Jejunal Angiodysplasia in an Elderly Patient with Aortic Stenosis: Significance of Von Willebrand Factor as an Etiologic Factor

Kubo T, Yoshii S, Yamano HO, Saito M, Sakata K, Sugita S, Hasegawa T, Horiuchi H, Nakase H

Intern Med 2022.11

COVID-19-associated disseminated mucormycosis: An autopsy case report

Daisuke Kyuno, Terufumi Kubo, Mitsuhiro Tsujiwaki, Shintaro Sugita, Michiko Hosaka, Hazuki Ito, Keisuke Harada, Akira Takasawa, Yusaku Kubota, Kumi Takasawa, Yusuke Ono, Kazufumi Magara, Eichi Narimatsu, Tadashi Hasegawa, Makoto Osanai

World Journal of Clinical Cases ( Baishideng Publishing Group Inc. ) 10 ( 28 ) 10358 - 10365 2022.10 [International journal]

BACKGROUND: Reports of mucormycosis, an infectious disease that commonly affects immunocompromised individuals, have increased during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Disseminated mucormycosis associated with COVID-19 is rare but fatal and is characterized by an aggressive clinical course and delayed diagnosis. Our report documents a case of disseminated mucormycosis after COVID-19 infection. This is a rare pathological autopsy report on COVID-19-associated mucormycosis. CASE SUMMARY: A 58-year-old man was transferred to our hospital with severe COVID-19 pneumonia. During treatment for acute respiratory distress syndrome, he developed intra-abdominal bleeding that required a right hemicolectomy and ileostomy for hemostasis. The ileostoma and surgical wound developed necrosis followed by sepsis and multi-organ failure, which led to death. An autopsy revealed multiple thrombi associated with Rhizopus oryzae infection, which led to the necrosis of multiple infected organs. CONCLUSION: Early suspicion and diagnosis followed by treatment are keys to better outcomes of mucormycosis in patients with severe COVID-19.

DOI PubMed

Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study

Kohichi Takada, Tomohiro Kubo, Junko Kikuchi, Makoto Yoshida, Ayako Murota, Yohei Arihara, Hajime Nakamura, Hiroyuki Nagashima, Hiroki Tanabe, Shintaro Sugita, Yumi Tanaka, Ayana Miura, Yoshihito Ohhara, Atsushi Ishiguro, Hiroshi Yokouchi, Yasuyuki Kawamoto, Yusuke Mizukami, Hirofumi Ohnishi, Ichiro Kinoshita, Akihiro Sakurai

Frontiers in Oncology ( Frontiers Media SA ) 12 988527 - 988527 2022.09 [International journal]

Characterization of the genomic landscape of biliary tract cancer (BTC) may lead to applying genotype-matched therapy for patients with this disease. Evidence that comprehensive cancer genomic profiling (CGP) guides genotype-matched therapy to improve clinical outcomes is building. However, the significance of CGP in patients with BTC remains unclarified in clinical practice. Therefore, the purposes of this study were to assess the utility of CGP and identify associations between clinical outcomes and genomic alterations in patients with BTC. In this prospective analysis, detection rates for actionable genomic alterations and access rates for genotype-matched therapy were analyzed in 72 patients with advanced BTC who had undergone commercial CGP. Cox regression analyses assessed relationships between overall survival and genomic alterations detected with CGP. The most common genomic alterations detected were TP53 (41, 56.9%), followed by CDKN2A/B (24, 33.3%/20, 27.8%), and KRAS (20, 27.8%). Actionable genomic alterations were identified in 58.3% (42/72) of patients. Detection rates for FGFR2 fusions, IDH1 mutations, and BRAF V600E were low in this cohort. Eight (11.1%) patients received genotype-matched therapy. For patients with intrahepatic cholangiocarcinoma (ICC), CDKN2A/B loss was associated with shorter overall survival. These real-world data demonstrate that CGP can identify therapeutic options in patients with advanced BTC. CDKN2A/B loss was identified as a poor prognostic factor in patients with ICC. Thus, this study provides a rationale for considering CGP in planning therapeutic strategies for advanced BTC.

DOI PubMed

Liver metastasis 13 years after the resection of a malignant triton tumor originating in the duodenum

Keita Ohashi, Yoh Asahi, Toshiya Kamiyama, Tatsuhiko Kakisaka, Tatsuya Orimo, Akihisa Nagatsu, Yuzuru Sakamoto, Hirofumi Kamachi, Tomofumi Takagi, Takuya Otsuka, Tomoko Mitsuhashi, Shintaro Sugita, Tadashi Hasegawa, Akinobu Taketomi

International Cancer Conference Journal ( Springer Science and Business Media LLC ) 11 ( 3 ) 178 - 183 2022.07 [International journal]

This is an additional case report of a malignant triton tumor arising in the duodenum that was removed by pancreatoduodenectomy. Liver and gallbladder dysfunctions were detected in a regular blood examination during a follow-up for hypertension in a 62-year-old woman with a previous surgical history for a malignant Triton tumor in the duodenum 13 years ago. Further examinations revealed a metastatic liver tumor originating from the malignant triton tumor in the duodenum. Since the progression of the liver tumor was detected after radiation therapy, complete resection was performed by right hepatectomy. Curative hepatectomy resulted in disease-free survival for 1 year and 5 months in an extremely rare case of liver metastasis derived from a malignant triton tumor in the duodenum.

DOI PubMed

Atypical spindle cell/pleomorphic lipomatous tumor with a sarcomatous component showing high mitotic activity and Ki-67 labeling index: report of a unique case mimicking dedifferentiated liposarcoma

Shintaro Sugita, Taro Sugawara, Makoto Emori, Tomoyuki Aoyama, Michiko Hosaka, Keiko Segawa, Hiromi Fujita, Tadashi Hasegawa

Medical Molecular Morphology ( Springer Science and Business Media LLC ) 2022.07

Authorship： Lead author

DOI

Difference in immunohistochemical findings among anti-PD-L1 antibodies and their relationships with CD4+ and CD8+ T cells in Japanese melanoma patients

Daisuke Yoneta, Junji Kato, Takafumi Kamiya, Kohei Horimoto, Sayuri Sato, Masahide Sawada, Tomoyuki Minowa, Tokimasa Hida, Shintaro Sugita, Hisashi Uhara

International Journal of Clinical Oncology ( Springer Science and Business Media LLC ) 27 ( 8 ) 1364 - 1371 2022.06 [Domestic journal]

BACKGROUND: The immunohistochemical evaluation of programmed death ligand 1 (PD-L1) is important for selecting treatments. Several antibodies are available for such evaluations, but data regarding the differences in the antibodies' positivity are limited in melanoma, particularly the acral and mucosal types. We investigated the differences in melanoma tissues' PD-L1 expression among the commonly used PD-L1 antibodies and then evaluated the relationship between PD-L1+ tumor cells and tumor-infiltrating lymphocytes (TILs). PATIENTS AND METHODS: We examined 56 primary lesions and 8 metastatic lymph node samples from 56 Japanese patients with melanoma (28 acral melanoma, 8 mucosal melanoma, 18 cutaneous melanoma, 2 unknown). Immunohistochemical staining was performed using three primary antibodies against PD-L1 (E1L3N, SP142, and 28-8). PD-L1-positive staining in tumor cells was defined as ≥ 1% expression. RESULTS: The positive rates were 25.0% for 28-8, 34.0% for E1L3N, and 34.0% for SP142 in 64 samples. The positive rates of acral melanoma were 10.7% for 28-8, 21.4% for E1L3N, and 21.4% for SP142. The positive rate of mucosal melanoma for which all three antibodies reacted was 12.5%. The positive rates of cutaneous melanoma were 55.6% for 28-8, 66.7% for E1L3N, and 66.7% for SP142. Significant relationships were observed among the PD-L1+ tumor cells, CD4+ TILs, and CD8+ TILs (p < 0.001). CONCLUSION: The staining results by E1L3N, SP142, and 28-8 antibodies were within the allowable range, although the positive rates by E1L3N and P142 were slightly higher than that of 28-8. CD4+ TILs and CD8+ TILs were quantitatively correlated with PD-L1-positive tumor cells.

DOI PubMed

Complete Response To Eribulin In A Patient With Unresectable Liposarcoma: A Case Report And Implications Of New Biomarkers

Nakamura H, Takada K, Emori M, Hayasaka N, Sugita S

Intern Med ( Japanese Society of Internal Medicine ) 2022.05

DOI

Diagnosis of prosthetic joint infection at the hip using the standard uptake value of three-phase 99mTc-hydroxymethylene diphosphonate SPECT/CT

Naoya Yama, Satoshi Nagoya, Shintaro Sugita, Masayuki Koyama, Masamitsu Hatakenaka

Annals of Nuclear Medicine ( Springer Science and Business Media LLC ) 36 ( 7 ) 634 - 642 2022.04 [Domestic journal]

PURPOSE: To retrospectively investigate whether the standard uptake value (SUV) of 99mTc-bone single-photon emission computed tomography (SPECT)/CT could be useful for predicting prosthetic joint infection (PJI) at the hip. PATIENTS AND METHODS: We analyzed the cases of 37 patients with a suspected PJI at the hip who underwent 99mTc-bone SPECT/CT and surgical intervention with pathological and bacterial examinations. We divided the cases into those with and those without a causative bacterium detected in a surgical specimen, i.e., the positive bacterial culture (PBC) group (n = 17) and negative bacterial culture (NBC) group (n = 20). Cases with neutrophilic infiltration of surgical specimen comprised the positive neutrophilic infiltration (PINF) group (n = 18) and those without INF comprised the non-neutrophilic infiltration (NINF) group (n = 19). Quantitative analyses were performed using maximum SUVs and peak SUVs of blood-pool (BP) phase images (SUVmaxBP and SUVpeakBP) and late (LT)-phase images (SUVmaxLT and SUVpeakLT). RESULTS: Regarding the bacterial cultures, there were significant differences between the PBC and NBC groups in SUVmaxBP (5.26 ± 1.49 vs. 4.21 ± 1.15, respectively; p = 0.019), SUVpeakBP (4.89 ± 1.32 vs. 3.87 ± 1.06, p = 0.012), SUVmaxLT (16.10 ± 6.36 vs. 11.67 ± 4.95, p = 0.026), and SUVpeakLT (14.58 ± 5.83 vs. 10.49 ± 4.31 p = 0.036). Regarding neutrophilic infiltration, there were significant differences between the PINF and NINF groups in SUVmaxBP (5.18 ± 1.48 vs. 4.24 ± 1.19, p = 0.047) and SUVpeakBP (4.78 ± 1.32 vs. 3.92 ± 1.10, p = 0.043). CONCLUSION: An SUV analysis of 99mTc-bone SPECT/CT is a useful method to differentiate a PJI at the hip from non-infection.

DOI PubMed

Feasibility of the semi-opened method of specimen resection for a circumferential resection margin in rectal cancer surgery: a multicenter study

Ichiro Takemasa, Koichi Okuya, Kenji Okita, Masayuki Ishii, Masaaki Ito, Kay Uehara, Tsuyoshi Konishi, Shigeki Yamaguchi, Masafumi Inomata, Shintaro Sugita, Tadashi Hasegawa, Atsushi Ochiai, Yoshiharu Sakai, Masahiko Watanabe

Surgery Today ( Springer Science and Business Media LLC ) 52 ( 9 ) 1275 - 1283 2022.04 [Domestic journal]

PURPOSE: A circumferential resection margin (CRM) > 1 mm is a surrogate marker of oncologic outcomes in rectal cancer patients. In Japan, because the mesentery is removed from the rectum, the CRM cannot be measured. This multicenter prospective study evaluates the feasibility of a resected specimen processing method that allows CRM measurement. METHODS: Fifty patients with rectal cancer were enrolled. Resected specimens were processed as previously reported. The primary outcomes were CRM measurement and the rate of CRM positivity. The secondary outcomes were the quality of total mesorectal excision, the possibility to visualize and sample the tumor, the number of harvested lymph nodes, and comparison between the pathological CRM and preoperative mesorectal fascia (MRF) involvement. This study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry under identification number UMIN000031735. RESULTS: The CRM was measurable in all patients and found to be positive in three (6%). We confirmed tumor localization, sampled the tumor, and measured the distal margin in all patients. A median of 20 lymph nodes were harvested. The concordance rate between preoperative MRF involvement and pathological CRM status was 90%. CONCLUSION: A semi-opened rectal specimen with transverse slicing is a feasible method for measuring the CRM.

DOI PubMed

Extensive mucosal sloughing of the small intestine and colon in a patient with severe COVID‐19

Tsukasa Yamakawa, Keisuke Ishigami, Ayumu Takizawa, Yumemi Takada, Sae Ohwada, Yoshihiro Yokoyama, Tomoe Kazama, Daisuke Hirayama, Shinji Yoshii, Hiro‐O Yamano, Rina Ohizumi, Naofumi Bunya, Taro Sugawara, Mitsuhiro Tsujiwaki, Shintaro Sugita, Satoshi Takahashi, Eichi Narimatsu, Hiroshi Nakase

DEN Open ( Wiley ) 2 ( 1 ) e42 2022.04 [International journal]

Patients with coronavirus disease 2019 (COVID-19) primarily cause respiratory symptoms. However, gastrointestinal (GI) symptoms can also occur. The endoscopic characteristics of the GI tract in COVID-19 patients remain unclear. We herein report a 62-year-old male with severe COVID-19 who needed multidisciplinary treatment, including extracorporeal membrane oxygenation (ECMO). Despite the improvement in his respiratory status, GI bleeding developed. Capsule endoscopy and colonoscopy revealed extensive mucosal sloughing in the lower intestinal tract. Additionally, we performed a comprehensive analysis of the mRNA expression levels of various proinflammatory cytokines in the intestinal mucosal tissues. The results suggested a significant elevation of IL-6, which could be involved in the pathophysiology of the GI involvement in COVID-19. Further investigation with more clinical data, including endoscopic findings and molecular analyses, will contribute to a comprehensive understanding of COVID-19-associated GI injury.

DOI PubMed

Primary cutaneous diffuse large B‐cell lymphoma, leg type, of the face that appeared on pre‐existing T‐cell pseudolymphoma clinically resembling actinic reticuloid

Yuna Hosokawa, Takafumi Kamiya, Shintaro Sugita, Tokimasa Hida, Kohichi Takada, Yasuyuki Sumikawa, Hiroyuki Takahashi, Hisashi Uhara

The Journal of Dermatology ( Wiley ) 49 ( 6 ) e206-e207 2022.03 [International journal]

DOI PubMed

A Case of Unresectable Combined Hepatocellular-Cholangiocarcinoma Successfully Treated with Lenvatinib

Osuga T, Miyanishi K, Ito R, Tanaka S, Hamaguchi K, Ohnuma H, Murase K, Takada K, Nagayama M, Kimura Y, Sugawara T, Sugita S, Takemasa I, Hasegawa T, Kato J

Case Rep Oncol 15 318 - 325 2022.03

Prognostic usefulness of a modified risk model for solitary fibrous tumor that includes the Ki-67 labeling index

Shintaro Sugita, Keiko Segawa, Noriaki Kikuchi, Tomoko Takenami, Tomomi Kido, Makoto Emori, Yukinori Akiyama, Kohichi Takada, Shiro Hinotsu, Tadashi Hasegawa

World Journal of Surgical Oncology ( Springer Science and Business Media LLC ) 20 ( 1 ) 29 - 29 2022.02 [International journal]

Authorship： Lead author

Abstract Background Predicting the prognosis of patients with solitary fibrous tumor (SFT) is often difficult. The prognostic risk models developed by Demicco et al. are now the standard for evaluating the risk of SFT metastasis in the current World Health Organization classification of soft tissue and bone tumors. Methods In this study, we examined the prognostic usefulness of a modified version of the Demicco risk models that replaces the mitotic count with the Ki-67 labeling index. We compared the three-variable and four-variable Demicco risk models with our modified risk models using Kaplan–Meier curves based on data for 43 patients with SFT. Results We found a significant difference in metastasis-free survival when patients were classified into low-risk and intermediate/high-risk groups using the three-variable (P = 0.022) and four-variable (P = 0.046) Demicco models. There was also a significant difference in metastasis-free survival between the low-risk and intermediate/high-risk groups when the modified three-variable (P = 0.006) and four-variable (P = 0.022) models were used. Conclusion Modified risk models that include the Ki-67 labeling index are effective for prediction of the prognosis in patients with SFT.

DOI PubMed

Scattered Media Elastic Fibers from the Aortic Root to the Ascending Aorta in a 30-Year-Old Marfan Syndrome Patient

Tomohiro Nakajima, Yutaka Iba, Syuichi Naraoka, Tsuyoshi Shibata, Shintaro Sugita, Nobuyoshi Kawaharada

Annals of Thoracic and Cardiovascular Surgery ( Editorial Committee of Annals of Thoracic and Cardiovascular Surgery ) 2022

DOI PubMed

Snapshots of lymphatic pathways in colorectal cancer surgery using near-infrared fluorescence, in vivo and ex vivo.

Yu Sato, Tetsuta Satoyoshi, Kenji Okita, Daisuke Kyuno, Atsushi Hamabe, Koichi Okuya, Toshihiko Nishidate, Emi Akizuki, Masayuki Ishii, Hiro-O Yamano, Shintaro Sugita, Hiroshi Nakase, Tadashi Hasegawa, Ichiro Takemasa

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 47 ( 12 ) 3130 - 3136 2021.12 [International journal]

INTRODUCTION: Indocyanine green (ICG) fluorescence imaging has been used for blood flow assessment in anastomoses in the field of colorectal cancer surgery. However, whether ICG fluorescence is related to the presence of cancer cells in the lymph nodes is unclear. We explored the utilization of ICG fluorescence in colorectal cancer surgery. MATERIALS AND METHODS: ICG was injected into the submucosa around the tumor before radical resection in colorectal cancer patients. Intraoperatively, near-infrared (NIR) fluorescence was used for lymphatic flow visualization. After specimen removal, harvested lymph nodes were classified as positive or negative based on the detection of fluorescence, followed by pathological examination. ICG distribution on a section of each lymph node was examined by fluorescence microscopy. RESULTS: Overall, 155 patients underwent real-time NIR fluorescence imaging-guided surgery. Altogether, 1,017 lymph nodes were retrieved from these patients. Metastatic lymph nodes were present in 36 (5.8%) of 622 fluorescence-negative lymph nodes, which was significantly higher than 11 (2.8%) of 395 fluorescence-positive lymph nodes (odds ratio: 2.15, P = 0.03). Fluorescence microscopy of metastatic lymph nodes showed that ICG fluorescence was present in the normal structural region but not in the cancerous region of the lymph nodes. Furthermore, ICG fluorescence was observed in all metastatic lymph nodes, except those with cancer cells occupying >90% of the total area. CONCLUSIONS: ICG fluorescence detected only the normal parts of the lymph node draining from the peritumoral area and not the cancer tissues. This finding is important for developing appropriate strategies for navigation surgery using NIR fluorescence.

DOI PubMed

Mediterranean fever gene-associated enterocolitis in an elderly Japanese woman.

Yasuhiro Shibata, Keisuke Ishigami, Tomoe Kazama, Toshiyuki Kubo, Hiro-O Yamano, Shintaro Sugita, Masaki Murata, Hiroshi Nakase

Clinical journal of gastroenterology 14 ( 6 ) 1661 - 1666 2021.12 [Domestic journal]

An 86-year-old woman was admitted to our hospital with anemia. She had never experienced symptoms of serositis. Colonoscopy revealed colitis with erosions and a friable mucosa. First, she was diagnosed with unclassified inflammatory bowel disease (IBD-U). We suspected familial Mediterranean fever as a differential diagnosis of IBD-U, and MEFV gene analysis showed heterozygosity for Exon2 R202Q. The patient was treated with colchicine 0.5 mg. After 4 months, a follow-up colonoscopy showed remarkable improvement of the mucosal inflammation throughout the entire colon. MEFV gene-associated enterocolitis responding to colchicine may be observed in patients with IBD-U and elucidating the role of MEFV gene mutations in intestinal inflammation is a future challenge.

DOI PubMed

Case of immunoglobulin (Ig)M/IgG immune complex vasculitis associated with multicentric Castleman's disease.

Aika Shionoya, Tokimasa Hida, Hiroshi Ikeda, Shintaro Sugita, Keiko Segawa, Tadashi Hasegawa, Hisashi Uhara

The Journal of dermatology 48 ( 12 ) e614-e615 2021.12 [International journal]

DOI PubMed

A modified method for resected specimen processing in rectal cancer: Semi-opened with transverse slicing for measuring of the circumferential resection margin.

Masayuki Ishii, Ichiro Takemasa, Kenji Okita, Koichi Okuya, Atsushi Hamabe, Toshihiko Nishidate, Emi Akizuki, Yu Sato, Ryo Miura, Takahiro Korai, Shintaro Sugita, Tadashi Hasegawa

Asian journal of endoscopic surgery 2021.11 [Domestic journal]

Circumferential resection margin (CRM) is essential for oncological quality assessment in rectal cancer surgery. CRM represents a surrogate parameter for oncological outcomes and is important for stratifying treatment strategies in Western nations. In Japan, the mesentery is removed for specimen processing in order to extract as many lymph nodes (LNs) as possible; consequently, CRM cannot be measured. Given the diversification of treatment strategies for rectal cancer, the lack of measurement of CRM to assess surgical outcomes is a crucial issue that must be resolved. Therefore, it is necessary to establish a method enabling measurement of CRM while enjoying the advantages of the Japanese method. In the method we developed, the mesentery is removed from the rectum more than 2 cm away from the tumor, and the vicinity of the tumor is circularized. It is necessary to investigate the usefulness of this method prospectively in a multi-center study.

DOI PubMed

Complete Response Induced by Concurrent Chemoradiotherapy in a Patient with NUT Carcinoma: A Case Report.

Joji Muramatsu, Kohichi Takada, Shintaro Sugita, Takaaki Tsuchiya, Keisuke Yamamoto, Masaru Takagi, Kazuyuki Murase, Saki Ameda, Yohei Arihara, Koji Miyanishi, Koh-Ichi Sakata, Junji Kato

Internal medicine (Tokyo, Japan) 2021.10 [Domestic journal]

An 18-year-old man presented with sudden vision loss in his left eye. Magnetic resonance imaging revealed a tumor that had invaded the left optic nerve, originating from the left posterior ethmoid sinus. Immunohistochemical analyses identified positive staining for NUT protein in the nuclei of tumor cells. We diagnosed locally advanced NUT carcinoma (NC) and initiated concurrent chemoradiotherapy (CCRT), consisting of chemotherapy with vincristine, doxorubicin, and cyclophosphamide, alternating with ifosphamide and etoposide, plus radiation therapy. The patient achieved a complete response. CCRT can be a useful treatment option for adolescent and young-adult patients with locally advanced unresectable NC.

DOI PubMed

Mixed neuroendocrine non-neuroendocrine neoplasm of the gallbladder complicated by a pancreaticobiliary maljunction of a non-dilated biliary duct: A case report.

Kohei Wagatsuma, Kotaro Akita, Masayo Motoya, Yasutoshi Kimura, Shintaro Sugita, Takehiro Hirano, Yujiro Kawakami, Yasunao Numata, Keisuke Ishigami, Yoshiharu Masaki, Ayako Murota, Masahiro Shitani, Noriyuki Akutsu, Shigeru Sasaki, Hiroshi Nakase

Medicine 100 ( 39 ) e27336 2021.10 [International journal]

RATIONALE: Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is a rare tumor. MiNEN of the gallbladder (GB) with pancreaticobiliary maljunction (PMJ) is extremely rare. The origin of MiNEN of the GB remains unknown; the biliary tract normally lacks neuroendocrine cells. MiNEN of the GB has a poor prognosis; because of its rarity, no treatment or management guidelines have been established yet. PATIENT CONCERNS: A 47-year-old male presenting with right hypochondrial pain and malaise for 3 months was referred to our hospital for further management. DIAGNOSIS: The neuron-specific enolase level was increased. Contrast-enhanced computed tomography revealed a mass of 70 mm in size with unclear boundaries in the liver. The GB was surrounded by this mass, narrowing the lumen of the GB. Many swollen lymph nodes were observed in the hepatoduodenal ligament. Endoscopic retrograde cholangiopancreatography revealed a PMJ with a non-dilated biliary duct. A percutaneous biopsy was performed on the liver mass, and the pathological findings were neuroendocrine carcinoma (NEC) (small cell type). We diagnosed a NEC of the GB, T3N1M0, stage IIIB (Union for International Cancer Control, 7th edition). INTERVENTIONS: Because of advanced lymph node metastasis, we considered this tumor difficult to cure solely by surgical intervention. After initial chemotherapy consisting of cisplatin and irinotecan, a marked reduction in both tumor and lymph node sizes enabled conversion surgery. The pathological diagnosis of the resected tumor was MiNEN consisting of NEC and adenocarcinoma. The primary lesion was the adenocarcinoma occupying the luminal side of the GB. As a postsurgical treatment, the patient received additional irradiation therapy to the common hepatic duct and liver stump because of positive surgical margins. OUTCOMES: At 13 months postoperatively, computed tomography findings revealed the appearance of a hypervascular liver tumor, and laboratory data showed increased serum neuron-specific enolase levels. Chemotherapy was unsuccessful, leading to the death of the patient 36 months from the date of diagnosis. LESSONS: There are several reports on the development of MiNEN of the GB. In our case, a PMJ-related adenocarcinoma of the GB transdifferentiated into NEC. Further accumulation of cases is necessary to establish a treatment strategy for MiNEN of the GB.

DOI PubMed

Ki-67 immunoexpression and radiological assessment of necrosis improves accuracy of conventional and modified core biopsy systems in predicting the final grade assigned to adult-soft tissue sarcomas. An international collaborative study.

Isidro Machado, Julia Cruz, Alberto Righi, Marco Gambarotti, Cristina Ferrari, Poosit Ruengwanichayakun, Francisco Giner, Nuria Rausell, Javier Lavernia, Shintaro Sugita, Laura Najera, Lola Suarez, Xavier Sanjuan, José Antonio Narváez García, Francisco Javier García Del Muro, M Carmen Gómez-Mateo, Manuel Moreno Valladares, Irma Ramos-Oliver, Cleofe Romagosa, Antonina Parafioriti, Armiraglio Elisabetta, Andrea di Bernardo, Samuel Navarro, Tadashi Hasegawa, Estanislao Arana, Antonio Llombart-Bosch

Pathology, research and practice 225 153562 - 153562 2021.09 [International journal]

Based on the French Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) grading system, this study assesses the accuracy of conventional and modified core biopsy (CB) systems in predicting the final grade (low vs high) assigned to the resected specimen. Substituting Ki-67 immunoexpression for mitotic count, and radiological for histological assessment of necrosis, we used two modified FNCLCC CB grading systems: (1) Ki-67 immunoexpression alone, and (2) Ki-67 plus radiological assessment of necrosis. We graded 199 soft tissue sarcomas (STS) from nine centers, and compared the results for the conventional (obtained from local histopathology reports) and modified CB systems with the final FNCLCC grading of the corresponding resected specimens. Due to insufficient sample quality or lack of available radiologic data, five cases were not evaluated for Ki67 or radiological assessment of necrosis. The conventional FNCLCC CB grading system accurately identified 109 of the 130 high-grade cases (83.8%). The CB grading matched the final FNCLCC grading (low vs high) in 175 (87.9%) of the 199 resected tumors; overestimating the final grade in three cases and underestimating in 21 cases. Modified system 1 (Ki-67) accurately identified 117 of the 130 high-grade cases (90.0%). The CB grading matched the final FNCLCC grading (low vs high) in 175 (89.7%) of the 195 evaluated cases; overestimating seven and underestimating 13 cases. Modified system 2 (Ki-67 plus radiological necrosis) accurately identified 120 of the 130 high-grade cases (92.3%). This last matched the final FNCLCC grading (low vs high) in 177 (91.2%) of the 194 evaluated cases; overestimating seven and underestimating 10 cases. Modified system 2 obtained highest area under ROC curves, although not statistically significant. Underestimated CB grades did not correlate with histological subtypes, although many of the discrepant cases were myxoid tumors (myxofibrosarcomas or myxoid liposarcomas), leiomyosarcomas or undifferentiated pleomorphic/spindle cell sarcomas. Using modified FNCLCC CB grading systems to replace conventional mitotic count and histologic assessment of necrosis may improve the distinction between low and high-grade STS on CB. Our study confirms that classifying grade 1 as low grade and grades 2 and 3 as high grade improves correlation between CB and final grade by up to 21%, irrespective of CB system used. A higher than expected Ki-67 score in a low-grade sarcoma diagnosed on CB should raise concern that a higher-grade component may not have been sampled. Furthermore, correlation of all clinicopathological and radiological findings at multidisciplinary meetings is essential to assess the histological grade on CB as accurately as possible.

DOI PubMed

Eribulin in combination with HER2-targeted antibodies for successful treatment of metastatic salivary duct carcinoma: A report of two cases.

Akihito Fujimi, Yasuhiro Nagamachi, Naofumi Yamauchi, Takuji Nishisato, Kazuyuki Murase, Kohichi Takada, Mitsuhiro Tsujiwaki, Shintaro Sugita, Tadashi Hasegawa, Junji Kato

Oral oncology 120 105287 - 105287 2021.09 [International journal]

DOI PubMed

Secondary malignant giant cell tumor of bone with histone H3.3 mutation: A case series.

Makoto Emori, Satoshi Nagoya, Masato Sugawara, Emi Mizushima, Junya Shimizu, Yasutaka Murahashi, Kazuyuki Murase, Kohichi Takada, Shintaro Sugita, Michiaki Takagi, Tadashi Hasegawa, Toshihiko Yamashita

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 26 ( 5 ) 926 - 930 2021.09 [Domestic journal]

DOI PubMed

Assessment of H3K27me3 immunohistochemistry and combination of NF1 and p16 deletions by fluorescence in situ hybridization in the differential diagnosis of malignant peripheral nerve sheath tumor and its histological mimics.

Shintaro Sugita, Tomoyuki Aoyama, Makoto Emori, Tomomi Kido, Tomoko Takenami, Kodai Sakuraba, Kotomi Terai, Taro Sugawara, Mitsuhiro Tsujiwaki, Tadashi Hasegawa

Diagnostic pathology 16 ( 1 ) 79 - 79 2021.08 [International journal]

Authorship： Lead author

BACKGROUND: A definitive diagnosis of malignant peripheral nerve sheath tumor (MPNST) is challenging, especially in cases without neurofibromatosis 1 (NF1), because MPNST lacks specific markers on immunohistochemistry (IHC). METHODS: We performed IHC for histone 3 trimethylated on lysine 27 (H3K27me3) and evaluated the percentage of cells with H3K27me3 loss using measured values at 10% intervals, categorized as complete loss (100% of tumor cells lost staining), partial loss (10% to 90% of tumor cells lost staining), and intact (no tumor cells lost staining). We conducted fluorescence in situ hybridization (FISH) for NF1 and p16 deletions comparing 55 MPNSTs and 35 non-MPNSTs, consisting of 9 synovial sarcomas (SSs), 8 leiomyosarcomas (LMSs), 10 myxofibrosarcomas (MFSs), and 8 undifferentiated pleomorphic sarcomas (UPSs). We assessed the percentage of cells with homozygous and heterozygous deletions and defined "deletion" if the percentage of either the NF1 or p16 deletion signals was greater than 50% of tumor cells. RESULTS: Among the 55 MPNSTs, 23 (42%) showed complete H3K27me3 loss and 32 (58%) exhibited partial loss or intact. One each of the 9 SSs (11%), 8 LMSs (12%), and 8 UPSs (12%) showed complete H3K27me3 loss and many non-MPNSTs exhibited intact or partial H3K27me3 loss. Among the 55 MPNSTs, 33 (60%) and 44 (80%) showed NF1 or p16 deletion, respectively. Co-deletion of NF1 and p16 was observed in 29 (53%) MPNSTs. Among the 23 MPNTSs showing H3K27me3 complete loss, 18 (78%) and 20 (87%) exhibited NF1 or p16 deletion, respectively. Among the 32 MPNSTs with H3K27me3 partial loss or intact, 15 (47%) and 24 (75%) exhibited NF1 or p16 deletion, respectively. The frequency of NF1 and/or p16 deletion tended to be lower in non-MPNSTs than in MPNSTs. Approximately 90% of MPNSTs included cases with H3K27me3 complete loss and cases showing H3K27me3 partial loss or intact with NF1 and/or p16 deletion. Approximately 50% of MPNSTs showed co-deletion of NF1 and p16 regardless of H3K27me3 loss. CONCLUSIONS: FISH for NF1 and p16 deletions, frequently observed in high-grade MPNSTs, might be a useful ancillary diagnostic tool for differentiating MPNST from other mimicking spindle cell and pleomorphic sarcomas.

DOI PubMed

Successful hemostasis of bleeding gastric inflammatory fibroid polyp by endoscopic treatment in a patient with severe COVID-19.

Ayako Murota, Shinji Yoshi, Ryu Okuda, Sae Oowada, Tsukasa Yamakawa, Tomoe Kazama, Daisuke Hirayama, Keisuke Ishigami, Hiro-O Yamano, Eichi Narimatu, Shintaro Sugita, Tadashi Hasegawa, Hiroshi Nakase

Clinical journal of gastroenterology 14 ( 4 ) 1008 - 1013 2021.08 [Domestic journal]

The coronavirus disease-2019 (COVID-19) has rapidly become a pandemic, resulting in a global suspension of non-emergency medical procedures such as screening endoscopic examinations. There have been several reports of COVID-19 patients presenting with gastrointestinal symptoms such as diarrhea and vomiting. In this report, we present a case of successful hemostasis of bleeding gastric inflammatory fibroid polyp by endoscopic treatment in a patient with severe COVID-19. The case was under mechanical ventilation with extracorporeal membrane oxygenation (ECMO), and the airway was on a closed circuit. This indicates that COVID-19 is associated with not only lung injury but also intestinal damage, and that proper protective protocols are essential in guaranteeing the best outcomes for patients and clinical professionals during this pandemic.

DOI PubMed

Expression of programmed cell death ligand 1 (PD-L1) at in situ and invasive extramammary Paget's disease and literature review.

Junji Kato, Shintaro Sugita, Kohei Horimoto, Sayuri Sato, Daisuke Yoneta, Masahide Sawada, Mao Fujioka, Tadashi Hasegawa, Hisashi Uhara

The Australasian journal of dermatology 62 ( 3 ) 412 - 414 2021.08 [International journal]

DOI PubMed

Fatal fulminant hepatitis induced by combined ipilimumab and nivolumab therapy despite favorable histologic response and confirmed by autopsy in a patient with clear cell renal cell carcinoma.

Terufumi Kubo, Taro Sugawara, Tomoyo Shinkawa, Tomoyo Kurisu, Nodoka Kouzen, Toshiaki Tanaka, Fumimasa Fukuta, Kouji Yamasaki, Shintaro Sugita, Kazuhiko Matsuo, Rena Morita, Yoshihiko Hirohashi, Tomohide Tsukahara, Takayuki Kanaseki, Tadashi Hasegawa, Naoya Masumori, Toshihiko Torigoe

Immunological medicine 44 ( 2 ) 136 - 141 2021.06 [International journal]

Effective management of immune-related adverse events in patients receiving immunotherapy for cancer is problematic. In this report, we present the case of a 58-year-old man with advanced clear cell renal cell carcinoma who responded well to a combination of ipilimumab and nivolumab. However, after two courses of treatment, he developed fulminant hepatitis and died. An autopsy confirmed that the primary lesion in the left kidney was more than 99% necrotic with only six small residual tumor lesions. These lesions were infiltrated by large numbers of CD8-positive/TIA-1-positive lymphocytes. However, a metastatic lesion in the right kidney harbored few lymphocytes. Furthermore, the tumor cells in the metastatic lesion and one of the residual lesions showed decreased expression of HLA class I molecules, which are a prerequisite for cytotoxic T-lymphocyte-mediated immunotherapy in tumor cells. In this patient, more than 80% of hepatocytes were destroyed and the parenchyma was infiltrated with CD8-positive/TIA-1-positive lymphocytes. The patient had polyuria, which was attributed to neurohypophysitis caused by the infiltration of CD8-positive/TIA-1-positive lymphocytes. We believe that this is an instructive case for immuno-oncologists.

DOI PubMed

Primary capicua transcriptional repressor-rearranged sarcoma of the lung.

Yasushi Mizukami, Yuki Takahashi, Shintaro Sugita, Kento Wakabayashi, Hiroaki Suzuki, Tadashi Hasegawa, Hiroko Noguchi, Hirofumi Adachi

Japanese journal of clinical oncology 51 ( 4 ) 654 - 656 2021.04 [International journal]

A 60-year-old man had a malignant left lower lung tumour with no metastases and underwent video-assisted thoracoscopic left lower lobectomy and lymphadenectomy. Pathological examination led to a diagnosis of capicua transcriptional repressor (CIC)-rearranged sarcoma. He has had 3.5 years of recurrence-free survival. CIC-rearranged sarcoma is a Ewing-like sarcoma that shows pathological findings similar to Ewing sarcoma. Most of CIC-rearranged sarcoma is CIC-double homeobox 4 protein (DUX4) fusion. Pulmonary CIC-rearranged sarcoma is extremely rare and has an unfavourable prognosis. However, complete resection can produce prognosis of long-term survival, and thus, surgery is an important option.

DOI PubMed

ALK-positive atypical Spitz tumour with conspicuous rosette-like structures.

Tomoyuki Minowa, Tokimasa Hida, Kohei Horimoto, Junji Kato, Takafumi Kamiya, Shintaro Sugita, Masashi Idogawa, Toshiaki Saida, Tadashi Hasegawa, Takashi Tokino, Hisashi Uhara

European journal of dermatology : EJD 31 ( 2 ) 256 - 258 2021.04 [International journal]

DOI PubMed

Multiple lung lesions in a 13-year-old girl with classical nodular sclerosis Hodgkin Lymphoma.

Shuhei Adachi, Akira Takebayashi, Kotoe Iesato, Keita Igarashi, Masaki Yamamoto, Tsukasa Hori, Yukihiko Kawasaki, Taijiro Mishina, Shintaro Sugita

International journal of hematology 113 ( 3 ) 318 - 319 2021.03 [Domestic journal]

DOI PubMed

Stroke Mimics and Chameleons from the Radiological Viewpoint of Glioma Diagnosis.

Ayaka Sasagawa, Takeshi Mikami, Yusuke Kimura, Yukinori Akiyama, Shintaro Sugita, Tadashi Hasegawa, Masahiko Wanibuchi, Nobuhiro Mikuni

Neurologia medico-chirurgica 61 ( 2 ) 134 - 143 2021.02 [Domestic journal]

Gliomas are sometimes difficult to differentiate from strokes and are often misdiagnosed on magnetic resonance imaging (MRI); thus, the terms "stroke mimics" and "stroke chameleons" have been introduced. In this study, we analyzed stroke mimics and stroke chameleons in glioma and discussed the diagnostic perplexity.We retrospectively reviewed cases that were removed from lesions that were considered to be brain tumors. This study enrolled 214 patients who underwent tumor resection for suspected glioma. Clinical characteristics and radiological findings of the patients were compared between the masquerade findings group, which was further divided into two groups: the stroke chameleons and stroke mimics according to their final diagnosis, and the intelligible findings group.Stroke chameleons and stroke mimics were significantly higher in age and smaller in lesion size than the intelligible findings group. In the multivariate analysis, the predictive factor of the masquerade finding group was higher age and smaller size. Stroke mimics group has a tendency to be higher rate of hyperintensity lesion on diffusion-weighted imaging (DWI) compared with stroke chameleons group. The average period from initial diagnosis to pathological diagnosis was 13.50 days in the stroke chameleons and 61.50 days in the stroke mimics, which proved significantly different.Proper diagnosis of glioma and stroke affects a patient's prognosis, and should be diagnosed as soon as possible. However, stroke mimics and stroke chameleons caused by glioma can occur. Thus, the diagnosis of a stroke should take into consideration the possibility of a glioma in real clinical situations.

DOI PubMed

[Probable Immunoglobulin G4 (IgG4)-related Periaortitis Requiring Differentiation from Mediastinal Tumor].

Yoshiki Chiba, Wataru Arai, Miho Ohkawa, Osamu Tada, Ryunosuke Maki, Taijiro Mishina, Masahiro Miyazima, Atsushi Watanabe, Shintaro Sugita

Kyobu geka. The Japanese journal of thoracic surgery 74 ( 2 ) 108 - 111 2021.02 [Domestic journal]

A 42-year-old man with a history of suspected of Behcet's disease underwent oral steroid treatment. During follow-up, chest X-ray revealed an abnormal shadow of the mediastinum. Chest computed tomography(CT) showed a circumferential tumor around the descending thoracic aorta. Enhanced CT showed a lowly and uniformly enhanced tumor at delay phase. A mediastinal tumor was suspected, which prompted a biopsy of the periaortic tumor by video-assisted thoracic surgery (VATS). Histopathological diagnosis showed numerous immunogloblin G4 (IgG4)-positive plasma cells suggesting the possibility of IgG4-related periaortitis. However, based on the diagnostic criteria, the case was comprehensively diagnosed as probable IgG4-related periaortitis, steroid treatment may have affected blood IgG4-positive cells and tissues.

PubMed

Response to 'Is the case really a SMARCA4-deficient thoracic sarcoma?'

Kohichi Takada, Shintaro Sugita, Tadashi Hasegawa

Thoracic cancer 12 ( 1 ) 141 - 141 2021.01 [International journal]

DOI PubMed

Arteriovenous malformation in the pancreatic head initially mimicking a hypervascular mass treated with duodenum-preserving pancreatic head resection: a case report.

Takahiro Korai, Yasutoshi Kimura, Masafumi Imamura, Minoru Nagayama, Ayumi Kanazawa, Ryo Miura, Takeshi Murakami, Daisuke Kyuno, Hiroshi Yamaguchi, Kotomi Terai, Shintaro Sugita, Takayuki Nobuoka, Tadashi Hasegawa, Ichiro Takemasa

Surgical case reports 6 ( 1 ) 301 - 301 2020.12 [International journal]

BACKGROUND: The mainstay treatment for arteriovenous malformation in the pancreatic head (Ph-AVM) is standard pancreatectomy, especially pancreaticoduodenectomy (PD), or interventional endovascular treatment. We report the first case of Ph-AVM treated with duodenum-preserving pancreatic head resection (DPPHR) performed to preserve the periampullary organs. CASE PRESENTATION: A 59-year-old man presenting with back pain underwent contrast-enhanced computed tomography followed by angiography of the anterior superior pancreaticoduodenal artery. He was diagnosed with Ph-AVM and indicated for DPPHR with preservation of the periampullary organs; Ph-AVM's benign nature seldom requires lymph node dissection. During the operation, the right colon was mobilized and the omental bursa was released to expose the periampullary structures. The pancreas was transected just above the superior mesenteric vein. The inferior pancreaticoduodenal artery and papillary arteries branching from the posterior superior pancreaticoduodenal artery were carefully preserved to maintain the blood flow to the lower bile duct and papilla of Vater. The remnant pancreas was reconstructed with pancreaticogastrostomy using the modified Blumgart method. Pathological examination of the resected specimen revealed an irregular course of the arteries and veins concomitant with marked dilation throughout the pancreatic head. The patient was pathologically diagnosed with Ph-AVM. He developed hematemesis caused by a rupture of the pseudoaneurysm on postoperative day 20 and underwent coil embolization. A bilio-enteric fistula and stenosis of the common bile duct were found and treated by placement of an endoscopic biliary stent. At the 8-month follow-up, the Ph-AVM had not recurred. CONCLUSIONS: Compared to PD, DPPHR confers the clinical benefit of preserving the periampullary organs, although further studies are needed to confirm this. Therefore, the choice of this procedure should be based on the surgical morbidities and long-term outcome of the patient.

DOI PubMed

Myoepithelioma of soft tissue and bone, and myoepithelioma-like tumors of the vulvar region: Clinicopathological study of 15 cases by PLAG1 immunohistochemistry.

Keiko Segawa, Shintaro Sugita, Tomoyuki Aoyama, Tomoko Takenami, Hiroko Asanuma, Yui Kojima, Yoshiaki Inayama, Tadashi Hasegawa

Pathology international 70 ( 12 ) 965 - 974 2020.12 [International journal]

Authorship： Corresponding author

We demonstrated the clinicopathological findings of 13 myoepitheliomas of soft tissue and bone (MESTBs) and two myoepithelioma-like tumors of the vulvar region (MELTVRs), focusing on the association between nuclear atypia and clinical course, and the utility of immunohistochemistry (IHC) of pleomorphic adenoma gene 1 (PLAG1) for the pathological diagnosis of these tumors. Of the 13 MESTBs, eight, one and four cases exhibited mild, moderate and severe nuclear atypia, respectively. Two cases with venous invasion showed severe nuclear atypia and both died of advanced disease. Two MELTVR cases showed moderate nuclear atypia and had no evidence of disease after surgery. On IHC, 12 of 13 (92.3%) MESTBs showed PLAG1 immunoreactivity and none of the MELTVRs expressed PLAG1. In addition, MELTVRs showed loss of INI1 expression. In contrast, all MESTBs retained INI1 expression. Fluorescence in situ hybridization detected EWSR1, FUS and PLAG1 rearrangement in 5 (38.5%), 0 (0%) and 2 (15.4%) of the 13 MESTBs, respectively. No EWSR1, FUS and PLAG1 rearrangement were observed in the METLVRs. In conclusion, MESTBs with both severe nuclear atypia and venous invasion would be indicative of malignant potential. PLAG1 might be a useful IHC marker in MESTB diagnosis.

DOI PubMed

Case series of three patients with hereditary diffuse gastric cancer in a single family: Three case reports and review of literature.

Masahiro Hirakawa, Kohichi Takada, Masanori Sato, Chisa Fujita, Naotaka Hayasaka, Takayuki Nobuoka, Shintaro Sugita, Aki Ishikawa, Miyako Mizukami, Hiroyuki Ohnuma, Kazuyuki Murase, Koji Miyanishi, Masayoshi Kobune, Ichiro Takemasa, Tadashi Hasegawa, Akihiro Sakurai, Junji Kato

World journal of gastroenterology 26 ( 42 ) 6689 - 6697 2020.11 [International journal]

BACKGROUND: Hereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome often associated with germline mutations in the CDH1 gene. However, the frequency of CDH1 mutations is low in patients with HDGC in East Asian countries. Herein, we report three cases of HDGC harboring a missense CDH1 variant, c.1679C>G, from a single Japanese family. CASE SUMMARY: A 26-year-old female (Case 1) and a 51-year-old male (father of Case 1), who had a strong family history of gastric cancer, were diagnosed with advanced diffuse gastric cancer. After genetic counselling, a 25-year-old younger brother of Case 1 underwent surveillance esophagogastroduodenoscopy that detected small signet ring cell carcinoma foci as multiple pale lesions in the gastric mucosa. Genetic analysis revealed a CDH1 c.1679C>G variant in all three patients. CONCLUSION: It is important for individuals suspected of having HDGC to be actively offered genetics evaluation. This report will contribute to an increased awareness of HDGC.

DOI PubMed

Surgically treated gastric melanoma of unknown primary: A case report from a 10-year survivor.

Toshiyuki Takahashi, Shintaro Sugita, Hidetoshi Kagaya, Takayuki Morita

Pathology international 70 ( 10 ) 786 - 792 2020.10 [International journal]

We describe an extremely rare case of simultaneous double melanoma of the stomach with no other obvious primary source. The patient has survived for more than 12 years post-complete gastrectomy. The patient was a woman in her seventies who was referred for anemia by another clinic. Esophagogastroscopy revealed an ulcerated gastric tumor that was diagnosed as a gastrointestinal stromal tumor (GIST) by endoscopic biopsy. She was admitted to our hospital for further examination and treatment. Gastroscopy at our institution revealed two submucosal tumors in the gastric wall. Since no metastatic lesions were detected after systemic exploration, multiple GIST of the stomach was diagnosed, and a total gastrectomy was performed. Malignant melanoma was diagnosed in both lesions by a histopathological study of the resected stomach. The patient's postoperative progress was good, and thorough examination of the skin did not result in the discovery of any systemic neoplastic lesions which could be regarded as the source for the primary tumor. No anticancer treatments were used. The patient has survived, with no recurrence for over ten years postsurgery. Strong evidence is presented in this case for the diagnosis and treatment of gastric malignant melanoma.

DOI PubMed

Osteofibrous dysplasia-like adamantinoma treated via intercalary segmental resection with partial cortex preservation using pedicled vascularized fibula graft: a case report.

Yuji Yamamura, Makoto Emori, Nobuyuki Takahashi, Mitsumasa Chiba, Junya Shimizu, Yasutaka Murahashi, Shintaro Sugita, Kousuke Iba, Tadashi Hasegawa, Toshihiko Yamashita

World journal of surgical oncology 18 ( 1 ) 203 - 203 2020.08 [International journal]

BACKGROUND: Morphologically, osteofibrous dysplasia-like adamantinoma is thought to be intermediate between osteofibrous dysplasia and adamantinoma. Its treatment is not well established owing to its rarity. CASE PRESENTATION: We report about of a 10-year-old girl with osteofibrous dysplasia-like adamantinoma initially diagnosed as osteofibrous dysplasia and treated via intercalary segmental resection with partial cortex preservation using a pedicled vascularized fibula graft for reconstruction. Bone union was observed 9 weeks after surgery. Twenty-two months after the definitive surgery, no recurrence was observed. CONCLUSION: This case illustrates the upgrade from osteofibrous dysplasia to osteofibrous dysplasia-like adamantinoma. The surgical method may aid the treatment of osteofibrous dysplasia-like adamantinoma with incomplete cortex involvement of the tumor.

DOI PubMed

Mucinous carcinoma originating in the peritoneum diagnosed by an ascites cell block: a case report.

Sachiko Nagao, Motoki Matsuura, Masato Tamate, Shintaro Sugita, Tsuyoshi Saito

Journal of medical case reports 14 ( 1 ) 99 - 99 2020.07 [International journal]

BACKGROUND: Peritoneal carcinoma is a rare disease that is diagnosed and treated in a manner similar to ovarian cancer. In most cases, the histological type is serous carcinoma, and chemotherapy is effective. However, there are a few case reports of mucinous peritoneal carcinoma. We inferred the histological type before surgery using an ascites cell block sample, which was useful for determining the treatment plan. CASE PRESENTATION: Our patient was a 60-year-old Japanese woman. She presented with a feeling of fullness in the abdomen. A computed tomographic scan showed a large quantity of ascitic fluid and thickening of the greater omentum, as well as thickening of the peritoneum at the pouch of Douglas and diaphragm. Hence, peritoneal carcinoma was suspected. The tumor markers carcinoembryonic antigen, cancer antigen 19-9, and cancer antigen 125 were all increased, and no malignant findings were observed in the uterus or ovaries. Cells suggestive of carcinoma were found in the ascitic fluid, and immunostaining by the cell block method suggested the possibility of mucinous carcinoma. The preoperative chemotherapy strategy was changed to short courses, and tumor reduction surgery was planned. Similar to the suspicion before surgery, the pathology results indicated mucinous carcinoma, and the therapeutic effect of chemotherapy was grade 0. CONCLUSIONS: Determining whether peritoneal carcinoma is serous carcinoma is important for therapy and prognostic prediction. In this case, we encountered a patient for whom surgery was chosen because of drug therapy resistance inferred through histological type estimation using the cell block method. Inferring the histological type by cell block preparation is useful for diagnosis and treatment selection.

DOI PubMed

Detection of VHL deletion by fluorescence in situ hybridization in extraneuraxial hemangioblastoma of soft tissue.

Keiko Segawa, Shintaro Sugita, Tomoyuki Aoyama, Seiichi Minami, Kazuo Nagashima, Masumi Tsuda, Shinya Tanaka, Tadashi Hasegawa

Pathology international 70 ( 7 ) 473 - 475 2020.07 [International journal]

Authorship： Corresponding author

DOI PubMed

Genetic analyses of mosaic neurofibromatosis type 1 with giant café-au-lait macule, plexiform neurofibroma and multiple melanocytic nevi.

Tokimasa Hida, Masashi Idogawa, Masae Okura, Shintaro Sugita, Taro Sugawara, Yasushi Sasaki, Takashi Tokino, Toshiharu Yamashita, Hisashi Uhara

The Journal of dermatology 47 ( 6 ) 658 - 662 2020.06 [International journal]

Neurofibromatosis type 1 (NF1) is a genodermatosis caused by heterozygous germ line variations in the NF1 gene. A second-hit NF1 aberration results in the formation of café-au-lait macules, cutaneous neurofibroma and plexiform neurofibroma (PNF). Mosaic NF1 (mNF1), caused by a postzygotic NF1 mutation, is characterized by localized or generalized NF1-related manifestations. Although NF1 and mNF1 are associated with pigmentary skin lesions, clinically recognizable melanocytic nevi that developed over PNF have not been reported. Here, we report the first case of multiple melanocytic nevi that developed on a giant café-au-lait macule and PNF. The PNF had biallelic NF1 deletions, a whole deletion of NF1 and a novel intragenic deletion involving exons 25-30. The deletions were not detected in the blood, which resulted in the diagnosis of mNF1. Furthermore, the nevus cells had not only biallelic NF1 deletions but also NRAS Q61R, a common mutation found in congenital melanocytic nevi. These analyses revealed the coexistence of the two different mosaic diseases, mNF1 and congenital melanocytic nevi. For a diagnosis of cases with atypical NF1-like symptoms, genetic analyses using blood and lesional tissues are useful and aid in genetic counseling.

DOI PubMed

Pulmonary metastasectomy is associated with prolonged survival among patients with bone and soft tissue sarcoma.

Junya Shimizu, Makoto Emori, Yasutaka Murahashi, Tomoko Sonoda, Taijiro Mishina, Masahiro Miyajima, Atsushi Watanabe, Shintaro Sugita, Kohichi Takada, Kazuyuki Murase, Tadashi Hasegawa, Toshihiko Yamashita

Molecular and clinical oncology 12 ( 5 ) 429 - 434 2020.05 [International journal]

The aim of the present study was to evaluate the survival impact of surgical resection among patients with pulmonary metastases from bone and soft tissue sarcomas. A total of 34 consecutive patients with ≤5 pulmonary metastases from bone and soft tissue sarcomas were retrospectively reviewed. The patients included 19 men and 15 women, with a median age of 64.0 years and a median follow-up of 14.5 months. The oncological outcome was compared between patients who underwent surgical and non-surgical treatment. A total of 22 patients underwent surgery and 12 patients did not undergo surgery. The surgery group had 3- and 5 year overall survival rates of 62 and 53%, respectively. None of the patients in the non-surgery group survived to 3 years. Compared with the non-surgery group, surgery achieved significantly better 3- and 5 year overall survival rates. Pulmonary metastasectomy was associated with significantly improved survival among patients who were aged <64 years (P=0.0155), as well as those who were aged ≥64 years (P=0.0444), which indicated that age was not associated with a difference in survival between the two groups. Therefore, pulmonary metastasectomy may improve the prognosis of patients with pulmonary metastases from bone and soft tissue sarcomas.

DOI PubMed

Molecular Aberrations Associated with Seizure Control in Diffuse Astrocytic and Oligodendroglial Tumors.

Hime Suzuki, Nobuhiro Mikuni, Shintaro Sugita, Tomoyuki Aoyama, Rintaro Yokoyama, Yuto Suzuki, Rei Enatsu, Yukinori Akiyama, Takeshi Mikami, Masahiko Wanibuchi, Tadashi Hasegawa

Neurologia medico-chirurgica 60 ( 3 ) 147 - 155 2020.03 [Domestic journal]

Diffuse astrocytic and oligodendroglial tumors are frequently associated with symptomatic epilepsy, and predictive seizure control is important for the improvement of patient quality of life. To elucidate the factors related to drug resistance of brain tumor-associated epilepsy from a pathological perspective. From January 2012 to October 2017, 36 patients diagnosed with diffuse astrocytic or oligodendroglial tumors were included. Assessment for seizure control was performed according to the Engel classification of seizures. Patient clinical, radiological, and pathological data were stratified based on the following 16 variables: age, sex, location of tumor, existence of the preoperative seizure, extent of resection, administration of temozolomide, radiation therapy, recurrence, Karnofsky performance scale, isocitrate dehydrogenase 1, 1p/19q co-deletion, Olig2, platelet-derived growth factor receptor alpha, p53, ATRX, and Ki67. These factors were compared between the well-controlled group and drug-resistant seizure group. Twenty-seven patients experienced seizures; of these, 14 cases were well-controlled, and 13 cases were drug-resistant. Neither clinical nor radiological characteristics were significantly different between these two groups, though p53 immunodetection levels were significantly higher, and the frequency of 1p/19q co-deletion was significantly lower in the group with drug-resistant seizures than in the well-controlled group. In the multivariate analysis, only one item was selected according to stepwise methods, and a significant difference was observed for p53 (OR, 21.600; 95% CI, 2.135-218.579; P = 0.009). Upregulation of p53 may be a molecular mechanism underlying drug resistant epilepsy associated with diffuse astrocytic and oligodendroglial tumors.

DOI PubMed

High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma.

Martin F Orth, Tilman L B Hölting, Marlene Dallmayer, Fabienne S Wehweck, Tanja Paul, Julian Musa, Michaela C Baldauf, Didier Surdez, Olivier Delattre, Maximilian M L Knott, Laura Romero-Pérez, Merve Kasan, Florencia Cidre-Aranaz, Julia S Gerke, Shunya Ohmura, Jing Li, Aruna Marchetto, Anton G Henssen, Özlem Özen, Shintaro Sugita, Tadashi Hasegawa, Takayuki Kanaseki, Stefanie Bertram, Uta Dirksen, Wolfgang Hartmann, Thomas Kirchner, Thomas G P Grünewald

Cancers 12 ( 3 ) 2020.03 [International journal]

Ewing sarcoma (EwS) is an aggressive cancer displaying an undifferentiated small-round-cell histomorphology that can be easily confused with a broad spectrum of differential diagnoses. Using comparative transcriptomics and immunohistochemistry (IHC), we previously identified BCL11B and GLG1 as potential specific auxiliary IHC markers for EWSR1-FLI1-positive EwS. Herein, we aimed at validating the specificity of both markers in a far larger and independent cohort of EwS (including EWSR1-ERG-positive cases) and differential diagnoses. Furthermore, we evaluated their intra-tumoral expression heterogeneity. Thus, we stained tissue microarrays from 133 molecularly confirmed EwS cases and 320 samples from morphological mimics, as well as a series of patient-derived xenograft (PDX) models for BCL11B, GLG1, and CD99, and systematically assessed the immunoreactivity and optimal cut-offs for each marker. These analyses demonstrated that high BCL11B and/or GLG1 immunoreactivity in CD99-positive cases had a specificity of 97.5% and an accuracy of 87.4% for diagnosing EwS solely by IHC, and that the markers were expressed by EWSR1-ERG-positive EwS. Only little intra-tumoral heterogeneity in immunoreactivity was observed for differential diagnoses. These results indicate that BCL11B and GLG1 may help as specific auxiliary IHC markers in diagnosing EwS in conjunction with CD99, especially if confirmatory molecular diagnostics are not available.

DOI PubMed

Pediatric angiomyxofibromatous tumor of the falx cerebri with locally destructive growth into the cranial bone.

Kentaro Tsuji, Takeo Nakaya, Kentaro Ashizawa, Fumihiro Arai, Noriyoshi Fukushima, Akira Gomi, Shintaro Sugita, Tadashi Hasegawa, Akira Tanaka

Pathology international 70 ( 2 ) 123 - 125 2020.02 [International journal]

DOI PubMed

Successful Treatment by Surgery and Lenvatinib of a Patient with Adrenal Metastasis of Papillary Thyroid Cancer.

Hajime Nakamura, Kohichi Takada, Kazuyuki Murase, Hiroki Sakamoto, Naotaka Hayasaka, Kazuma Ishikawa, Yuki Ikeda, Makoto Yoshida, Satoshi Iyama, Ko Kobayashi, Tetsuya Shindo, Shintaro Sugita, Koji Miyanishi, Masayoshi Kobune, Naoya Masumori, Junji Kato

Case reports in oncological medicine 2020 2107430 - 2107430 2020 [International journal]

Papillary thyroid cancer (PTC) is considered an indolent cancer, but some PTC patients do present with distant metastases and treatment strategies for such patients are not well established. Recently, lenvatinib, an inhibitor of multiple tyrosine kinases, has been introduced to treat patients with advanced PTC but carries a risk of serious adverse events such as hemorrhage. Here, we report a PTC patient with a left adrenal metastasis and lenvatinib-induced hemorrhage who underwent successful surgical resection and was subsequently treated with a lower dose of lenvatinib. The patient has now been in a stable state with no adverse events for nearly two years. This case highlights the importance of surgical resection of metastatic PTC and subsequent lenvatinib therapy, even when the tumor is at an advanced stage.

DOI PubMed

Exceptionally rapid response to pembrolizumab in a SMARCA4-deficient thoracic sarcoma overexpressing PD-L1: A case report.

Kohichi Takada, Shintaro Sugita, Kazuyuki Murase, Tomoki Kikuchi, Ginji Oomori, Ryo Ito, Naotaka Hayasaka, Koji Miyanishi, Satoshi Iyama, Hiroshi Ikeda, Masayoshi Kobune, Makoto Emori, Junji Kato, Tadashi Hasegawa

Thoracic cancer 10 ( 12 ) 2312 - 2315 2019.12 [International journal]

SMARCA4-deficient thoracic sarcoma (SMARCA4-DTS) is a new clinical entity characterized by SMARCA4 inactivation and has a dismal prognosis because of rapid growth. Effective treatments for SMARCA4-DTS have not yet been developed. Most recently, anti-programmed cell death 1 receptor (PD-1) blockade has been effective for SMARCA4-deficient lung cancer and malignant rhabdoid tumor-like tumors. Here, we describe a patient with SMARCA4-DTC who experienced a marked response to the administration of pembrolizumab. A 70-year-old female was referred to our department for treatment of SMARCA4-DTC. Positron emission tomography-computed tomography had revealed a left mediastinal tumor, peritoneal dissemination and multiple cutaneous metastases at diagnosis. Immunohistochemical analyses revealed 60% of tumor cells expressed programmed cell death ligand 1 (PD-L1). The patient was given pembrolizumab as first-line treatment. Pembrolizumab suppressed tumor growth dramatically, with only one dose leading to a partial response. Our case suggests the immunohistochemical analysis of PD-L1 expression be undertaken for patients with SMARCA4-DTS and that pembrolizumab treatment may be a promising strategy for PD-L1-positive SMARCA4-DTS.

DOI PubMed

Agminated fibroblastic connective tissue nevus in a 1-year-old boy.

Marie Ohata, Susumu Fujiwara, Ai Yoshioka, Hiroshi Nagai, Shintaro Sugita, Nozomi Yamano, Yusuke Inoue, Chikako Nishigori

Pediatric dermatology 36 ( 6 ) 997 - 998 2019.11 [International journal]

DOI PubMed

Pneumothorax as an Adverse Event in Patients with Lung Metastasis of Soft Tissue Sarcoma under Eribulin Treatment.

Kohichi Takada, Kazuyuki Murase, Hajime Nakamura, Naotaka Hayasaka, Yohei Arihara, Satoshi Iyama, Hiroshi Ikeda, Makoto Emori, Shintaro Sugita, Katsuyuki Nakamura, Koji Miyanishi, Masayoshi Kobune, Junji Kato

Internal medicine (Tokyo, Japan) 58 ( 20 ) 3009 - 3012 2019.10 [Domestic journal]

Pneumothorax has been reported as a pazopanib-associated adverse event in patients with lung metastases of soft tissue sarcoma (STS). However, pneumothorax triggered by eribulin treatment has never been reported. We herein report two cases of spontaneous pneumothorax in patients with STS treated with eribulin. Both patients experienced pneumothorax accompanied by sudden dyspnea on day 9 or 10 of eribulin treatment. These two cases suggest that spontaneous pneumothorax may occur as an adverse event of eribulin treatment in such patients. We should therefore be alert for the potential development of pneumothorax during eribulin treatment of patients with STS and lung metastases.

DOI PubMed

Total Resection of Unilateral Adult-onset Xanthogranuloma of the Orbit via a Transcranial Orbital Approach.

Tomoaki Tamada, Masahiko Wanibuchi, Hime Suzuki, Rintaro Yokoyama, Yusuke Kimura, Ken Yamashita, Mitsuhiro Tsujiwaki, Shintaro Sugita, Yukinori Akiyama, Takeshi Mikami, Tadashi Hasegawa, Nobuhiro Mikuni

NMC case report journal 6 ( 4 ) 121 - 124 2019.10 [Domestic journal]

Adult orbital xanthogranuloma is rare and usually associated with systemic disease. There are several options available to treat this disorder. Periorbital lesions are treated with steroids, chemotherapy, radiotherapy, or local excision; however, there is still no consensus regarding optimal treatment. Here, we report a rare case of orbital xanthogranuloma that was not associated with systemic disease and was treated by transcranial surgery. The patient was a 52-year-old man who presented with a 2-year history of unilateral eye symptoms. A computed tomography scan revealed a well-defined mass in the right orbit. The mass was completely removed via a transcranial orbital approach. The histopathologic diagnosis was xanthogranuloma. No recurrence was observed during 15 months of postoperative follow-up. Complete surgical resection might be an effective treatment option for locally growing sporadic adult xanthogranulomatous disease of the orbit, and allows systemic steroids, chemotherapy, and irradiation to be avoided.

DOI PubMed

Spindle cell rhabdomyosarcoma in a lumbar vertebra with FUS-TFCP2 fusion.

Yohei Tagami, Shintaro Sugita, Terufumi Kubo, Noriyuki Iesato, Makoto Emori, Kohichi Takada, Mitsuhiro Tsujiwaki, Keiko Segawa, Taro Sugawara, Tomoki Kikuchi, Tadashi Hasegawa

Pathology, research and practice 215 ( 8 ) 152399 - 152399 2019.08 [International journal]

Authorship： Corresponding author

A 70-year-old woman developed severe buttock pain that progressed to a walking disturbance. Radiographs and computed tomography scans revealed an osteolytic lesion with osteosclerosis extending from the body to the arch of the fifth lumbar vertebra. Magnetic resonance imaging showed multinodular masses in the fifth lumbar vertebral body extending into the spinous processes and right transverse process. The masses were hypointense to isointense on T1-weighted images and hypointense to hyperintense on T2-weighted images. Histologic examination of biopsy specimens showed destruction of the trabecula of the vertebral bone by a fascicular and solid proliferation of spindle tumor cells and scattered rhabdomyoblasts, in a fibrotic background. The tumor cells were immunoreactive for keratins, vimentin, desmin, MyoD1, myogenin, and anaplastic lymphoma kinase. Fluorescence in situ hybridization detected split signals for FUS and TFCP2 in 80% and 64% of the tumor cells, respectively, suggesting FUS-TFCP2 fusion. Reverse transcription-polymerase chain reaction revealed a FUS-TFCP2 fusion. The final diagnosis was spindle cell rhabdomyosarcoma of a lumbar vertebra with a FUS-TFCP2 fusion. A spindle cell rhabdomyosarcoma with a FUS-TFCP2 fusion in a vertebral bone is rare and should be differentiated from metastatic carcinoma, particularly in the elderly.

DOI PubMed

Desmoplastic small round cell tumor of the parotid gland-report of a rare case and a review of the literature.

Kanako C Hatanaka, Emi Takakuwa, Yutaka Hatanaka, Akira Suzuki, Satoshi IIzuka, Nayuta Tsushima, Tomoko Mitsuhashi, Shintaro Sugita, Akihiro Homma, Shojiroh Morinaga, Tadashi Hashegawa, Yoshihiro Matsuno

Diagnostic pathology 14 ( 1 ) 43 - 43 2019.05 [International journal]

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare soft tissue tumor that generally involves the retroperitoneum, pelvis, omentum and mesentery in younger patients. However, extra-abdominal DSRCT is very rare. CASE PRESENTATION: A 49-year-old Japanese man noticed a mass in the right parotid gland. Ultrasound examination revealed a solid tumor about 2 cm in diameter. Computed tomography (CT) of the whole body revealed no other tumors or lymph node swelling. Superficial parotidectomy was performed. Histologically, the tumor was composed of various-sized tumor cell nests in an abundant fibromyxoid and collagenous background. The tumor cells were small to medium-sized. Immunohistochemistry showed that the tumor cells were immunoreactive for epithelial markers and desmin. They also showed strong nuclear staining with a Wilms tumor 1 (WT1) antibody detecting the C-terminal region (C-WT1), but not the N-terminal region (N-WT1). We also performed 3'/5' expression imbalance assay based on reverse transcription polymerase chain reaction (RT-PCR) to determine whether aberrant WT1 gene expression was present. This tumor was found to lack 5'-regional expression of the WT1 gene, as well as immunoreactivity with the N-WT1 antibody. Finally, fluorescence in situ hybridization (FISH) and RT-PCR analyses revealed the presence of a gene showing fusion between exon 7 of EWSR1 and exon 8 of WT1. The tumor was diagnosed as a DSRCT of the right parotid gland. The patient has been followed for 3 years without recurrence or metastasis. CONCLUSIONS: Although DSRCT in the salivary gland is extremely rare, it should be included in the differential diagnosis of poorly differentiated salivary gland neoplasms, especially with a fibromyxoid background. Pathologists should bear in mind that DSRCT may occur in major salivary glands and should perform immunohistochemistry with appropriate antibodies, not only those against keratin and desmin, but also one detecting the C-terminal region of WT-1. Furthermore, molecular detection of EWSR1-WT1 fusion gene conclusively confirmed the diagnosis of DSRCT in this uncommon location.

DOI PubMed

Pseudoaneurysm presenting around polytetrafluoroethylene fiber following microvascular decompression: A case report and literature review.

Tomoaki Tamada, Takeshi Mikami, Syoichi Komura, Hime Suzuki, Ryo Ukai, Shintaro Sugita, Tadashi Hasegawa, Nobuhiro Mikuni

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 63 231 - 234 2019.05 [International journal]

We report the first case of pseudoaneurysm associated with polytetrafluoroethylene fiber used in microvascular decompression (MVD). A 62-year-old female who had undergone MVD for hemifacial spasm 30 years ago presented with a 4-month history of progressive facial palsy. Computed tomography angiography revealed a large thrombosed aneurysm originating from the right posterior inferior cerebellar artery and having a mass effect upon the pons. The aneurysm was treated by trapping and bypass procedure. Intraoperatively, the pseudoaneurysm adhered to the dura mater, and the thrombus contained a large amount of polytetrafluoroethylene fiber. The cause and management of pseudoaneurysm after MVD is discussed.

DOI PubMed

Imprint cytology of biphenotypic sinonasal sarcoma of the paranasal sinus: A case report.

Shintaro Sugita, Terufumi Kubo, Tomoyuki Aoyama, Jun Moriya, Tsuyoshi Okuni, Masahiko Wanibuchi, Ken Yamashita, Maki Onodera, Mitsuhiro Tsujiwaki, Keiko Segawa, Taro Sugawara, Tadashi Hasegawa

Diagnostic cytopathology 47 ( 5 ) 507 - 511 2019.05 [International journal]

Authorship： Lead author

Biphenotypic sinonasal sarcoma (BSNS) is a rare low-grade spindle cell sarcoma that predominantly affects middle-aged women with multiple tumors in the sinonasal tract. BSNS shows biphenotypic expression of neural and myogenic markers on immunohistochemistry (IHC) with a specific chimeric PAX3-MAML3 fusion. The cytological features of BSNS have so far not been reported. Here, we describe a case of BSNS including findings of imprint cytology, histology, IHC, and genetic analysis. A 30-year-old woman presented with a nodular tumor that completely occupied the ethmoid sinus. The tumor was resected and submitted for imprint cytology, which revealed relatively bland spindle tumor cells that had mildly enlarged oval to spindle-shaped nuclei with fine nuclear chromatin and a thin nuclear rim in a clear background. Nucleoli were inconspicuous and there was no significant nuclear atypia and pleomorphism. These cytological findings were consistent with the histology of low-grade spindle cell sarcoma in BSNS. On IHC, the tumor cells were focally positive for S-100 protein and α-smooth muscle actin; nuclear β-catenin expression was also seen. PAX3 split signals were detected in 52% of tumor cells by fluorescence in situ hybridization. Reverse transcriptase-polymerase chain reaction also identified a chimeric PAX3-MAML3 fusion gene. Based on these findings, we diagnosed the tumor as BSNS. Our findings revealed that a relatively bland spindle cell cytology with a clear background is a characteristic feature of BSNS. BSNS should therefore be differentiated from benign and bland-appearing malignant spindle cell tumors and the combination of cytology, histology, IHC, and genetic analysis facilitates the diagnosis of BSNS.

DOI PubMed

Combination of eribulin plus AKT inhibitor evokes synergistic cytotoxicity in soft tissue sarcoma cells.

Naotaka Hayasaka, Kohichi Takada, Hajime Nakamura, Yohei Arihara, Yutaka Kawano, Takahiro Osuga, Kazuyuki Murase, Shohei Kikuchi, Satoshi Iyama, Makoto Emori, Shintaro Sugita, Tadashi Hasegawa, Akira Takasawa, Koji Miyanishi, Masayoshi Kobune, Junji Kato

Scientific reports 9 ( 1 ) 5759 - 5759 2019.04 [International journal]

An activated AKT pathway underlies the pathogenesis of soft tissue sarcoma (STS), with over-expressed phosphorylated AKT (p-AKT) correlating with a poor prognosis in a subset of STS cases. Recently, eribulin, a microtubule dynamics inhibitor, has demonstrated efficacy and is approved in patients with advanced/metastatic liposarcoma and breast cancer. However, mechanisms of eribulin resistance and/or insensitivity remain largely unknown. In this study, we demonstrated that an increased p-AKT level was associated with eribulin resistance in STS cells. We found a combination of eribulin with the AKT inhibitor, MK-2206, synergistically inhibited STS cell growth in vivo as well as in vitro. Mechanistically, eribulin plus MK-2206 induced G1 or G2/M arrest by down-regulating cyclin-dependent kinases, cyclins and cdc2, followed by caspase-dependent apoptosis in STS cells. Our findings demonstrate the significance of p-AKT signaling for eribulin-resistance in STS cells and provide a rationale for the development of an AKT inhibitor in combination with eribulin to treat patients with STS.

DOI PubMed

Early Lymph Node Metastasis May Predict Poor Prognosis in Soft Tissue Sarcoma.

Makoto Emori, Hiroyuki Tsuchie, Hiroyuki Nagasawa, Tomoko Sonoda, Arihiko Tsukamoto, Junya Shimizu, Yasutaka Murahashi, Emi Mizushima, Kohichi Takada, Kazuyuki Murase, Kotoe Iesato, Keita Igarashi, Tsukasa Hori, Masaki Yamamoto, Shintaro Sugita, Naohisa Miyakoshi, Tadashi Hasegawa, Yoichi Shimada, Toshihiko Yamashita

International journal of surgical oncology 2019 6708474 - 6708474 2019 [International journal]

Background: Lymph node metastasis (LNM) is a relatively rare event in soft tissue sarcoma. An association between the timing of LNM detection and patient prognosis is presently unknown. Patients and Methods: We retrospectively analyzed the clinicopathological features of 33 patients with LNM between 2001 and 2015. Analysis of the timing of LNM diagnosis was grouped according to patients presenting LNM in either <8 months (the median time from primary tumor diagnosis to LNM) or ≥8 months after primary tumor diagnosis. Results: A relationship between the primary tumor size and the timing of the LNM was not significantly found (Rs = 0.0088, p=0.96). Sixteen patients had an LNM detection duration of <8 months, and 17 patients had a duration of ≥8 months. The 5-year survival for patients with an LNM detection duration of <8 months and ≥8 months was 19% and 71%, respectively (p=0.0016). There were 19 patients with pulmonary metastases. Among them, there were 13 patients with a duration of primary tumor diagnosis to LNM of <8 months and 6 with a duration of ≥8 months (p=0.01). Conclusion: Early LNM (<8 months) may predict poor prognosis in soft tissue sarcoma.

DOI PubMed

Trastuzumab-Based Combination Chemotherapy in Patients with Human Epidermal Growth Factor Receptor-2-Positive Metastatic Carcinoma ex Pleomorphic Adenoma

Yohei Arihara, Kazuyuki Murase, Kohichi Takada, Naotaka Hayasaka, Shogo Miura, Koji Miyanishi, Masayoshi Kobune, Makoto Kurose, Yukinori Akiyama, Shintaro Sugita, Junji Kato

Case Reports in Oncology ( S. Karger AG ) 11 ( 3 ) 835 - 841 2018.12 [International journal]

Background: Carcinoma ex pleomorphic adenoma (CXPA) is a rare histologic subtype of lacrimal gland and submandibular gland cancer. Currently, there is no standard treatment for metastatic CXPA, although some case reports have explored the role of targeted agents in chemotherapy. A few histopathologic analyses have shown that some of these tumors overexpress human epidermal growth factor receptor-2 (HER2), suggesting a potential role for HER2-based therapy. We report here two cases of metastatic CXPA that were treated with trastuzumab-based chemotherapy (IRB approved) with rapid and significant responses. Case Report 1: A 66-year-old male was diagnosed as HER2-positive CXPA of the right lacrimal gland with multiple bone and lymph node metastases. Combination chemotherapy with trastuzumab (Tmab) and nanoparticle albumin-bound paclitaxel (nabPTX) was initiated. A rapid response was confirmed, and after seven cycles of treatment, CR(complete response) was achieved. Case Report 2: A 67-year-old female was diagnosed with HER2 positive CXPA of the right submandibular gland. Multiple pulmonary metastatic lesions were detected after surgery, and combination chemotherapy with Tmab and nab-PTX was initiated. A rapid partial response (PR) was confirmed, and she eventually became disease-free. Conclusion: In the absence of definitive clinical trials, which are unlikely to be performed due to the rarity of HER2-positive CXPA, therapeutic information must be obtained from case reports. Some reports, such as this one, have suggested a potential utility of trastuzumab-based chemotherapy.

DOI PubMed

Vertebral canal invasion of cervical lipoblastoma in childhood: A case report

Akira Takebayashi, Tsukasa Hori, Masaki Yamamoto, Kotoe Iesato, Keita Igarashi, Naoki Hatakeyama, Yukinori Akiyama, Masahiko Wanibuchi, Shintaro Sugita, Yoshiyuki Sakai, Minami Yoda, Hiroyuki Tsutsumi

Iranian Journal of Pediatrics ( Kowsar Medical Publishing Company ) 28 ( 6 ) 2018.12

Introduction: Lipoblastoma is a benign tumor that originates in the embryonal fat. This tumor can arise from various anatomical sites such as the extremities, trunk, and neck, but it rarely invades the spinal canal. Case Presentation: We describe a 3-year-old girl with a dumbbell-shaped lipoblastoma that extended into the cervical spine. Although she had no neurological deficit, we performed semi-total resection for decompression to the cord and avoid torticollis. Although a residual tumor was present, she recovered well and developed no neurological sequelae. We have selected a wait-and-see strategy for the residual tumor. She is now well-being more than four-years after the surgery. Conclusions: Early surgical intervention and decompression of the tumor was effective to avoid neurological defects.

DOI

Efficacy of liquid-based genetic diagnosis of endometrial cancer.

Motoki Matsuura, Kiyoshi Yamaguchi, Masato Tamate, Seiro Satohisa, Mizue Teramoto, Masahiro Iwasaki, Shintaro Sugita, Tadashi Hasegawa, Rika Koubo, Kiyoko Takane, Tsuneo Ikenoue, Yoichi Furukawa, Tsuyoshi Saito

Cancer science 109 ( 12 ) 4025 - 4032 2018.12 [International journal]

Although liquid-based cytology (LBC) has increased the sensitivity of cytological diagnosis of endometrial cancer (EC) compared with conventional smear cytology, the sensitivity of LBC for the detection of EC is between 70% and 96% and remains unsatisfactory. In the present study, we compared the efficacy of LBC with liquid-based genetic diagnosis (LBGDx) by amplicon sequencing of five genes including PTEN, PIK3CA, CTNNB1, KRAS, and TP53 in 48 LBC subjects who underwent endometrial screening. Consequently, LBC classified 15 samples as "positive or suspicious for malignancy" and the 15 were later confirmed as EC. However, LBC failed to identify five cases who were diagnosed as EC by additional transvaginal ultrasound and endometrial curettage, indicating that the sensitivity of cytology alone was 75% (15/20). LBGDx identified 11 pathogenic PTEN variants in 10 subjects, six PIK3CA variants in nine, three CTNNB1 variants in five, two KRAS variants in four, and three TP53 variants in three. Collectively, at least one pathogenic variant was identified in 19 subjects, which included 17 EC (15 endometrioid carcinoma and 2 endometrial carcinosarcomas), and one cervical adenocarcinoma. However, LBGDx did not identify any pathogenic mutations in three of the 20 EC, indicating that the sensitivity of LBGDx alone was 85% (17/20). Although five EC were negative for malignancy by LBC and three were negative for pathogenic mutations by LBGDx, the combination of LBC and LBGDx would successfully diagnose all 20 EC. These data suggested that LBGDx is a useful strategy to improve the sensitivity of screening of EC by LBC.

DOI PubMed

Influence of PD-L1 expression in immune cells on the response to radiation therapy in patients with oropharyngeal squamous cell carcinoma.

Yuki Fukushima, Masanori Someya, Kensei Nakata, Masakazu Hori, Mio Kitagawa, Tomokazu Hasegawa, Takaaki Tsuchiya, Toshio Gocho, Hikaru Ikeda, Yoshihiko Hirohashi, Toshihiko Torigoe, Shintaro Sugita, Tadashi Hasegawa, Tetsuo Himi, Koh-Ichi Sakata

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 129 ( 2 ) 409 - 414 2018.11 [International journal]

BACKGROUND AND PURPOSE: To investigate influences of proteins involved with tumor immunity on outcomes of radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC). MATERIAL AND METHODS: We performed immunohistochemical staining to examine expressions of p16 and proteins involved with tumor immunity in 92 OPSCC patients treated with radiotherapy. RESULTS: Patients with abundant infiltrating CD8-positive cells had the significantly better overall survival (OS) rate than patients with fewer CD8-positive cells (p = 0.026). Patients with higher PD-L1 expression in tumor cells (TC 1-3) had a better outcome than those with low PD-L1 expression in tumor cells (TC 0) for both OS (p = 0.019) and progression-free survival (PFS) rate (p = 0.032). Patients with high PD-L1 expression in infiltrating immune cells (IC 3) showed significantly better OS (p = 0.009) and PFS (p = 0.011) than those with low PD-L1 expression (IC 0-2). Patients with p16-negative and IC 3 showed similar OS to patients with p16-positive and IC 0-2. P16-positive tumors had a significantly higher CD8-positive cell infiltration and PD-L1 expression in tumor cells than p16-negative tumors. CONCLUSIONS: In addition to tumor p16 expression, PD-L1 expression in TC and IC can be useful for predicting the response of OPSCC to radiotherapy.

DOI PubMed

Detection of specific gene rearrangements by fluorescence in situ hybridization in 16 cases of clear cell sarcoma of soft tissue and 6 cases of clear cell sarcoma-like gastrointestinal tumor.

Keiko Segawa, Shintaro Sugita, Tomoyuki Aoyama, Terufumi Kubo, Hiroko Asanuma, Taro Sugawara, Yumika Ito, Mitsuhiro Tsujiwaki, Hiromi Fujita, Makoto Emori, Tadashi Hasegawa

Diagnostic pathology 13 ( 1 ) 73 - 73 2018.09 [International journal]

Authorship： Corresponding author

BACKGROUND: Clear cell sarcoma of soft tissue (CCSST) and clear cell sarcoma-like gastrointestinal tumor (CCSLGT) are malignant mesenchymal tumors that share some pathological features, but they also have several different characteristics. They are well known to express chimeric fusions of Ewing sarcoma breakpoint region 1 (EWSR1) and cAMP response element-binding protein (CREB) family members; namely, EWSR1-activating transcription factor 1 (ATF1) and EWSR1-CREB1. In addition, recent studies have suggested the presence of other fusions. METHODS: We used fluorescence in situ hybridization to detect specific rearrangements including EWSR1, ATF1, CREB1, and cAMP response element modulator (CREM) in 16 CCSST and 6 CCSLGT cases. We also used reverse transcription polymerase chain reaction (RT-PCR) to detect specific chimeric fusions of EWSR1-ATF1 and EWSR1-CREB1 using fresh tumor samples in available cases. RESULTS: A total of 15 of 16 CCSST cases (93.8%) had EWSR1 rearrangement, of which 11 (68.8%) also had ATF1 rearrangement, suggestive of the presence of EWSR1-ATF1 fusions. One CCSST case (6.3%) was found to have EWSR1 and CREM rearrangements, and 4 of 6 CCSLGT cases (66.7%) had EWSR1 rearrangement, of which 2 (33.3%) showed ATF1 rearrangement and the other 2 cases (33.3%) showed CREB1 rearrangement. These cases most likely had EWSR1-ATF1 and EWSR1-CREB1 fusions, respectively. RT-PCR was performed in 8 available cases, including 6 CCSSTs and 2 CCSLGTs. All CCSSTs showed EWSR1-ATF1 fusions. Among the 2 CCSLGT cases, one had EWSR1-ATF1 fusion and the other had EWSR1-CREB1 fusion. CONCLUSIONS: Rearrangements of EWSR1 and ATF1 or EWSR1-ATF1 fusion were predominantly found in CCSST, whereas those of EWSR1 and CREB1 or EWSR1-CREB1 tended to be detected in CCSLGT. A novel CREM fusion was also detected in a few cases of CCSST and CCSLGT. The cases in which EWSR1 rearrangement was detected without definitive partner genes should be considered for the presence of CREM rearrangement.

DOI PubMed

Systematic identification of cancer-specific MHC-binding peptides with RAVEN

Michaela C. Baldauf, Julia S. Gerke, Andreas Kirschner, Franziska Blaeschke, Manuel Effenberger, Kilian Schober, Rebeca Alba Rubio, Takayuki Kanaseki, Merve M. Kiran, Marlene Dallmayer, Julian Musa, Nurset Akpolat, Ayse N. Akatli, Fernando C. Rosman, Özlem Özen, Shintaro Sugita, Tadashi Hasegawa, Haruhiko Sugimura, Daniel Baumhoer, Maximilian M. L. Knott, Giuseppina Sannino, Aruna Marchetto, Jing Li, Dirk H. Busch, Tobias Feuchtinger, Shunya Ohmura, Martin F. Orth, Uwe Thiel, Thomas Kirchner, Thomas G. P. Grünewald

OncoImmunology ( Informa UK Limited ) 7 ( 9 ) e1481558 - e1481558 2018.09 [International journal]

Immunotherapy can revolutionize anti-cancer therapy if specific targets are available. Immunogenic peptides encoded by cancer-specific genes (CSGs) may enable targeted immunotherapy, even of oligo-mutated cancers, which lack neo-antigens generated by protein-coding missense mutations. Here, we describe an algorithm and user-friendly software named RAVEN (Rich Analysis of Variable gene Expressions in Numerous tissues) that automatizes the systematic and fast identification of CSG-encoded peptides highly affine to Major Histocompatibility Complexes (MHC) starting from transcriptome data. We applied RAVEN to a dataset assembled from 2,678 simultaneously normalized gene expression microarrays comprising 50 tumor entities, with a focus on oligo-mutated pediatric cancers, and 71 normal tissue types. RAVEN performed a transcriptome-wide scan in each cancer entity for gender-specific CSGs, and identified several established CSGs, but also many novel candidates potentially suitable for targeting multiple cancer types. The specific expression of the most promising CSGs was validated in cancer cell lines and in a comprehensive tissue-microarray. Subsequently, RAVEN identified likely immunogenic CSG-encoded peptides by predicting their affinity to MHCs and excluded sequence identity to abundantly expressed proteins by interrogating the UniProt protein-database. The predicted affinity of selected peptides was validated in T2-cell peptide-binding assays in which many showed binding-kinetics like a very immunogenic influenza control peptide. Collectively, we provide an exquisitely curated catalogue of cancer-specific and highly MHC-affine peptides across 50 cancer types, and a freely available software (https://github.com/JSGerke/RAVENsoftware) to easily apply our algorithm to any gene expression dataset. We anticipate that our peptide libraries and software constitute a rich resource to advance anti-cancer immunotherapy.

DOI PubMed

Bacillus Calmette-Guérin may have clinical benefit for glandular or squamous differentiation in non-muscle invasive bladder cancer patients: retrospective multicenter study.

Wakako Yorozuya, Naotaka Nishiyama, Tetsuya Shindo, Yuki Kyoda, Naoki Itoh, Shintaro Sugita, Tadashi Hasegawa, Naoya Masumori

Japanese journal of clinical oncology 48 ( 7 ) 661 - 666 2018.07 [International journal]

Objectives: To clarify the efficacy of intravesical Bacillus Calmette-Guérin (BCG) instillation for non-muscle invasive bladder (NMIBC) cancer with variant histology, especially glandular differentiation or squamous differentiation. Materials and methods: From May 1991 through June 2016, 53 patients were diagnosed retrospectively as having NMIBC with variant histology. Among these patients, 47 NMIBC patients with squamous differentiation or glandular differentiation were analyzed for this study. The median follow-up interval from diagnosis of NMIBC with variant histology was 28.9 months (1.5-168.8). Results: Of these patients, 38 (80.9%) and 9 (19.1%) were diagnosed as having glandular differentiation and squamous differentiation, respectively. Radical cystectomy was conducted for six (12.8%) immediately after the diagnosis of NMIBC with variant histology. Of the 41 patients with bladder preservation, 20 (48.8%), 3 (7.3%), 3 (7.3%) and 15 (36.6%) underwent BCG, THP, MMC and no additional treatment, respectively. There were significant differences between BCG and other treatments or no additional treatment for recurrence (P = 0.034), progression (P = 0.004) and cancer-specific survival (P = 0.014). Conclusion: Overall, our results show that intravesical BCG instillation for variant histology in NMIBC leads to a better prognosis with regard to progression and cause-specific survival than other intravesical treatments or no additional treatment. BCG treatment may also have a clinical benefit for variant histology in non-muscle invasive bladder cancer patients.

DOI PubMed

Cytokeratin 19 expression is a risk factor for metastasis in cutaneous squamous cell carcinoma

J. Kato, T. Hida, S. Sugita, T. Hasegawa, S. Kamiya, K. Horimoto, S. Sato, M. Sawada, H. Uhara

Journal of the European Academy of Dermatology and Venereology ( Blackwell Publishing Ltd ) 32 ( 7 ) e299 - e301 2018.07

DOI

Development of moyamoya disease after non-herpetic acute limbic encephalitis: A case report.

Yasuhiro Takahashi, Takeshi Mikami, Hime Suzuki, Katsuya Komatsu, Daisuke Yamamoto, Shun Shimohama, Kiyohiro Houkin, Shintaro Sugita, Tadashi Hasegawa, Nobuhiro Mikuni

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 53 250 - 253 2018.07 [International journal]

We report a case of moyamoya disease (MMD), which developed after non-herpetic acute limbic encephalitis (NHALE) associated with anti-leucine-rich glioma-inactivated 1 (LGI1) antibody. The patient's mother had a history of MMD. No vascular lesions were identified at the time of the NHALE. Nine years later, the patient visited our hospital due to memory disturbances and repeated transient ischemic attacks affecting the right limb. Diffusion-weighted magnetic resonance imaging revealed scattered areas of signal hyperintensity, and the patient was ultimately diagnosed with MMD based on angiography. Revascularization surgery was performed on the left side, where cerebral blood flow was impaired on 123I-N-isopropyl-p-iodoamphetamine single photon emission computed tomography. Postoperatively, the patient was discharged with a normal neurological examination. NHALE associated with LGI1 antibodies is an autoimmune disease. Although autoimmune disease is the most frequent finding other than atherosclerosis in quasi-MMD, this is the first report of NHALE associated with anti-LGI1 antibodies mimicking quasi-MMD. Inflammation and angiogenesis may contribute to the development of MMD, in addition to genetic background.

DOI PubMed

[p40 Negative Basaloid Squamous Cell Carcinoma of the Lung;Report of a Case].

Ryunosuke Maki, Shintaro Sugita, Yusuke Ono, Masahiro Miyajima, Makoto Tada, Yuki Takahashi, Taijirou Mishina, Atsushi Watanabe

Kyobu geka. The Japanese journal of thoracic surgery 71 ( 7 ) 547 - 550 2018.07 [Domestic journal]

Immunohistochemical staining is important for the differential diagnosis of basaloid squamous cell carcinoma(BSC)and other similar carcinomas, such as small-cell carcinomas and large-cell neuroendocrine carcinomas. p40 is a useful marker of squamous cell carcinoma that can be used for the diagnosis of BSC. We present the case of a 64-year-old man who was referred to our hospital for investigation of an abnormal shadow revealed on chest radiography. Computed tomography(CT) revealed a 16×11 mm nodule in the left lung(S1+2), and a thoracoscopic left upper lobectomy was performed. Histologically, lobular pattern with peripheral palisading was observed and the immunohistochemical staining revealed the tumor cells to be positive for p63 and negative for both p40 and neuroendocrine markers, leading to the diagnosis of BSC.

PubMed

Hepatic portal venous gas due to polystyrene sulfonate-induced enteritis.

Toshiyuki Kubo, Kentaro Yamashita, Yoshihiro Yokoyama, Daisuke Hirayama, Tomohiro Shirata, Kei Mitsuhashi, Kei Onodera, Eiichiro Yamamoto, Katsuhiko Nosho, Hiroo Yamano, Terufumi Kubo, Shintaro Sugita, Tadashi Hasegawa, Hiroshi Nakase

Clinical journal of gastroenterology 11 ( 3 ) 220 - 223 2018.06 [Domestic journal]

A 78-year-old man with acute right lower abdominal pain and nausea was referred to our hospital. Computed tomography (CT) demonstrated hepatic portal venous gas and a thickened wall of the terminal ileum, and colonoscopy demonstrated ulcers and erosions of the ileocecal region. Histological examination of biopsy samples revealed basophilic crystals consistent with the component of calcium polystyrene sulfonate (CPS). This patient started taking CPS 2 months prior for chronic hyperkalemia. The symptoms resolved soon after ceasing CPS, and subsequent imaging studies confirmed the disappearance of the portal venous gas and ileocolitis.

DOI PubMed

Giant cell-rich osteosarcoma of the vertebra with murine double minute chromosome 2- and cyclin-dependent kinase 4-positive and histone H3F3A mutant p.Gly34Trp-negative immunophenotypes.

Yumika Ito, Shintaro Sugita, Keiko Segawa, Taro Sugawara, Mitsuhiro Tsujiwaki, Hiromi Fujita, Yusuke Ono, Tomonori Morita, Makoto Emori, Tadashi Hasegawa

Pathology international 68 ( 5 ) 324 - 326 2018.05 [International journal]

Authorship： Corresponding author

DOI PubMed

Colonic inflammatory fibroid polyp with PDGFRA expression.

Taro Sugawara, Shintaro Sugita, Masatoshi Tateno, Akira Yabutani, Keiko Segawa, Yumika Ito, Mitsuhiro Tsujiwaki, Hiromi Fujita, Yusuke Ono, Tadashi Hasegawa

Pathology international 68 ( 3 ) 205 - 206 2018.03 [International journal]

Authorship： Corresponding author

DOI PubMed

Re-evaluation of MIB-1 immunostaining for diagnosing hyalinizing trabecular tumour of the thyroid: semi-automated techniques with manual antigen retrieval are more accurate than fully automated techniques.

Nami Takada, Mitsuyoshi Hirokawa, Chiho Ohbayashi, Takeshi Nishikawa, Tomoo Itoh, Naoko Imagawa, Tetsunari Oyama, Tadashi Handa, Tadashi Hasegawa, Shintaro Sugita, Akiko Murata, Akira Miyauchi

Endocrine journal 65 ( 2 ) 239 - 244 2018.02 [Domestic journal]

Hyalinizing trabecular tumour (HTT) immunohistochemically shows cell membranous immunoreactivity for MIB-1. This aberrant immunoreactivity is an important factor for the diagnosis of HTT. However, fully automated stainers frequently fail to confirm the immunoreactivity. The aim of this study is to investigate the cause of false negative cell membranous immunoreactivity for MIB-1 in HTT using fully automated stainers, to determine potential reasons for the problem, and to establish methods confirming cell membranous immunoreactivity for MIB-1 in HTT. Six participating institutions examined immunoreactivity for MIB-1 in 10 HTT cases using two approaches: fully automated and semi-automated methods. In the latter, antigen retrieval was carried out using manual methods adopted for routine assays at each institute. The autostainers used included the BOND-MAX, BOND-III, Benchmark XT, and Omnis systems. Using fully automated methods, institute E showed cell membranous MIB-1 positivity in all HTT cases. In contrast, at institute D, all HTT cases were negative. The positive rates of the remaining four institutes ranged from 10% to 20%. The incidence of positive cases using semi-automated methods was 100%, 90%, 90%, 30%, 80%, and 100% at institutes A, B, C, D, E, and F, respectively. We assert that antigen retrieval should be conducted manually for diagnosis of HTT; furthermore, definitively diagnosed HTT should be prepared as the external positive control.

DOI PubMed

Multiple gastrointestinal stromal tumors involving extragastrointestinal sites in neurofibromatosis type 1.

Keiko Segawa, Shintaro Sugita, Taro Sugawara, Yumika Ito, Mitsuhiro Tsujiwaki, Hiromi Fujita, Yusuke Ono, Kou Kobayashi, Megumi Hirobe, Makoto Yoshida, Tadashi Hasegawa

Pathology international 68 ( 2 ) 142 - 144 2018.02 [International journal]

Authorship： Corresponding author

DOI PubMed

Image analysis is an excellent tool for quantifying Ki-67 to predict the prognosis of gastrointestinal stromal tumor patients.

Shintaro Sugita, Hiroshi Hirano, Yutaka Hatanaka, Hiromi Fujita, Terufumi Kubo, Noriaki Kikuchi, Yumika Ito, Taro Sugawara, Keiko Segawa, Hiroyuki Hisai, Kentaro Yamashita, Takayuki Nobuoka, Yoshihiro Matsuno, Tadashi Hasegawa

Pathology international 68 ( 1 ) 7 - 11 2018.01 [International journal]

Authorship： Lead author

We investigated the quantification of Ki-67 staining using digital image analysis (IA) as a complementary prognostic factor to the modified National Institutes of Health (NIH) classification in patients with gastrointestinal stromal tumor (GIST). We examined 92 patients, focusing on the correlation between age, sex, primary tumor site, tumor size, predominant histologic type, mitotic index, modified NIH classification (low/intermediate vs high), Ki-67 quantitation, and recurrence-free survival (RFS). We compared two IA processes for whole slide imaging (WSI) and manually captured image (MCI) methods. A Ki-67 quantitation cutoff was determined by receiver operator characteristics curve analysis. In the survival analysis, the high-risk group of a modified NIH classification, a mitotic count >5 per 20 high-powered fields, and Ki-67 cutoffs of ≥6% and ≥8% obtained by IA of the WSI and MCI methods, respectively, had an adverse impact on RFS. On multivariate analysis, each Ki-67 quantitation method strongly predicted prognosis, more strongly than the modified NIH classification. In addition, Ki-67 quantitation using IA of the MCI method could stratify low or intermediate risk and high risk GIST patients. Thus, IA is an excellent tool for quantifying Ki-67 to predict the prognosis of GIST patients, and this semiautomated approach may be preferable for patient care.

DOI PubMed

Occult ovarian clear-cell carcinoma diagnosed as primary adenocarcinoma of the lung: A case report of a diagnostic pitfall for clinicians and pathologists.

Terufumi Kubo, Yoshihiko Hirohashi, Hiromi Fujita, Shintaro Sugita, Yasuhiro Kikuchi, Tomoyo Shinkawa, Munehide Nakatsugawa, Mitsuhiro Tsujiwaki, Yuta Sudo, Yuichiro Asai, Yasuaki Umeda, Hiroki Takahashi, Tadashi Hasegawa, Toshihiko Torigoe

Respiratory medicine case reports 25 306 - 308 2018 [International journal]

We present a case of ovarian clear-cell carcinoma that was initially diagnosed as adenocarcinoma of lung origin. This is an instructive diagnostic pitfall for clinicians and pathologists because of the unusual clinical course, small biopsy material, and noteworthy immunophenotype of the carcinoma. Imaging analysis identified only lung and liver lesions. In addition, the biopsy specimen from the lung was TTF-1 negative and napsin A positive, which is still possible for cancer of lung origin. Postmortem examination found that the cancer should be classified as ovarian clear-cell carcinoma distinguished by positive staining for napsin A and paired-box gene 8 (PAX8). Although PAX8 may not be usually investigated when tumoral lesions are identified in only the lung and liver, it is important to keep the necessity of PAX8 in mind to excluding carcinoma of Müllerian, renal, or thyroid origin.

DOI PubMed

Imprint cytology of clear cell sarcoma-like tumor of the gastrointestinal tract in the small intestine: A case report.

Takashi Kato, Shin Ichihara, Hiroko Gotoda, Shunji Muraoka, Terufumi Kubo, Shintaro Sugita, Tadashi Hasegawa

Diagnostic cytopathology 45 ( 12 ) 1137 - 1141 2017.12 [International journal]

Clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLGT) is an extremely rare malignant neoplasm in the digestive tract. Its cytomorphologic features have never previously been reported. Here, we describe a case of CCSLGT, including its cytologic examination findings. A 47-year-old woman presented with a mass in the small intestine, which was resected and sent for imprint cytology. Imprint smears revealed tumor cells with light eosinophilic or clear cytoplasm in a necrotic background. Many of the tumor cells were arranged in a perivascular growth with a pseudopapillary formation, and there were some non-neoplastic osteoclast-like giant cells. Histological examination revealed solid nests and a pseudopapillary pattern of the tumor cells with clear or pale eosinophilic cytoplasm and large nuclei with small nucleoli. Immunohistochemistry showed positive for vimentin, S-100, and SOX-10, and negative for SMA, c-KIT, cytokeratin, HMB-45, and MelanA. The EWSR1 gene split signal was detected by reverse transcriptase fluorescence in situ hybridization, and EWSR1-CREB1 gene fusion was indicated by reverse transcriptase polymerase chain reaction analysis. From these findings, we diagnosed the tumor as CCSLGT. To best of our knowledge, this is the first description of the imprint cytology features of CCSLGT.

DOI PubMed

Diagnostic utility of automated SureFISH (Dako Omnis) in the diagnosis of musculoskeletal translocation-related sarcomas.

Shintaro Sugita, Tomoyuki Aoyama, Yoshimasa Ito, Hiroko Asanuma, Taro Sugawara, Keiko Segawa, Yumika Ito, Noriaki Kikuchi, Mitsuhiro Tsujiwaki, Hiromi Fujita, Yusuke Ono, Tadashi Hasegawa

Pathology international 67 ( 10 ) 510 - 513 2017.10 [International journal]

Authorship： Lead author

Fluorescence in situ hybridization (FISH) is an essential tool for genetic diagnosis in daily pathological work. Almost full automation of FISH can be achieved with the recently released automated SureFISH platform (Dako Omnis, Agilent Technologies, Santa Clara, CA, USA). Its utility has been reported in HER2 amplification of breast and gastric carcinoma and ALK-rearranged lung cancer. Here, we examined the utility of automated SureFISH for the identification of rearrangement signals in translocation-related sarcomas (TRSs), including 11 EWSR1-rearranged and 10 synovial sarcoma cases, compared with non-automated conventional FISH using the same specimens. The percentages of EWSR1 or SS18 split signals were higher in automated SureFISH than in conventional FISH in 13 of the 21 cases. On the other hand, 8 of the 21 cases showed the same or lower percentage of split signals in automated SureFISH. Both FISH approaches detected EWSR1 and SS18 split signals in more than 10% of tumor cells in all cases. The strongest advantage of automated SureFISH is its ability to reduce running time without sacrificing quality. Other advantages include improved signal sharpness with oligo probes and reduced ecological toxicity by avoiding formamide use. Automated SureFISH is an excellent tool for the genetic diagnosis of TRSs and contributes to their rapid definitive diagnosis.

DOI PubMed

Practical use and utility of fluorescence in situ hybridization in the pathological diagnosis of soft tissue and bone tumors.

Shintaro Sugita, Tadashi Hasegawa

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 22 ( 4 ) 601 - 612 2017.07 [Domestic journal]

Authorship： Lead author

During routine pathological examination, fluorescence in situ hybridization (FISH) plays a significant role in the genetic analysis of samples. FISH can detect genetic abnormalities such as chromosomal translocations, gene amplifications, and deletions in formalin-fixed, paraffin-embedded (FFPE) specimens. Due to its practical advantages, FISH is already used in many pathology laboratories. It is especially useful for the diagnosis of translocation-related sarcomas (TRSs), which comprise about 25% of soft tissue sarcomas. Because TRSs have specific chimeric genes derived from characteristic chromosomal translocations, their diagnosis would not be possible without FISH. FISH significantly contributes to the genetic confirmation of TRS. Analysis using next-generation sequencing (NGS), the latest powerful method for comprehensive genomic analysis, has recently revealed many kinds of chromosomal translocations in various TRSs. We often use experimental results to create custom probes for FISH and have applied NOCA2 split probes and CIC split, CIC-FOXO4 fusion probes to the pathological diagnosis of soft tissue angiofibroma and CIC-rearranged sarcoma, respectively. Some chimeric fusions detected by NGS induce the expression of related proteins and their detection using immunohistochemistry is beneficial for pathological diagnosis. We previously identified characteristic FOSB expression in pseudomyogenic hemangioendothelioma (PHE) with a specific SERPINE1-FOSB fusion, revealing the usefulness of FOSB immunohistochemistry in the differential diagnosis of PHE and its mimics. Finally, we participated in a central review of a clinical trial of trabectedin monotherapy. We guaranteed an accurate diagnosis by using FISH and genetic confirmation to select appropriate TRS patients and thereby confirm the accuracy of the patient enrollment of the clinical trial. FISH is an essential tool for the pathological diagnosis of soft tissue and bone tumors. It can detect various genetic abnormalities in an "in situ" fashion using FFPE specimens on glass slides during routine examination. It is also an excellent tool for translating the latest experimental findings to practical use in routine pathological diagnosis. Further instrumental improvements in FISH will help it to become the universal method for the genetic analysis of pathological diagnoses.

DOI PubMed

NUTM2A-CIC fusion small round cell sarcoma: a genetically distinct variant of CIC-rearranged sarcoma.

Shintaro Sugita, Yasuhito Arai, Tomoyuki Aoyama, Hiroko Asanuma, Wakako Mukai, Natsuko Hama, Makoto Emori, Tatsuhiro Shibata, Tadashi Hasegawa

Human pathology 65 225 - 230 2017.07 [International journal]

Authorship： Lead author

CIC-rearranged sarcoma is a new entity of undifferentiated small round cell sarcoma characterized by chimeric fusions with CIC rearrangement. We report a NUTM2A-CIC fusion sarcoma in a 43-year-old woman who died of rapidly progressive disease. Histologic analysis revealed multinodular proliferation of small round tumor cells with mild nuclear pleomorphism. The sclerotic fibrous septa separated the tumor into multiple nodules. Immunohistochemistry showed that the tumor cells were diffusely positive for vimentin, focally positive for cytokeratin, and negative for CD99 and NKX2.2. Tumor cells were also negative for ETV4, which was recently identified as a specific marker for CIC-rearranged sarcoma. High-throughput RNA sequencing of a formalin-fixed, paraffin-embedded clinical sample unveiled a novel NUTM2A-CIC fusion between NUTM2A exon 7 and CIC exon 12, and fluorescence in situ hybridization identified CIC and NUTM2A split signals. This case shared several clinicopathological findings with previously reported CIC-rearranged cases. We recognized the tumor as a genetically distinct variant of CIC-rearranged sarcomas with a novel NUTM2A-CIC fusion.

DOI PubMed

Ovarian high-grade endometrioid stromal sarcoma with YWHAE and NUTM2B rearrangements.

Noriaki Kikuchi, Shintaro Sugita, Katsuya Nakanishi, Taro Sugawara, Keiko Segawa, Yumika Ito, Terufumi Kubo, Hiromi Fujita, Hiroshi Hirano, Ryoichi Tanaka, Tsuyoshi Saito, Tadashi Hasegawa

Pathology international 67 ( 6 ) 327 - 329 2017.06 [International journal]

Authorship： Corresponding author

DOI PubMed

Hepatitis C virus reactivation due to antiemetic steroid therapy during treatment of hepatocellular carcinoma.

Yutaka Kawano, Koji Miyanishi, Satoshi Takahashi, Tomohiro Kubo, Kazuma Ishikawa, Shintaro Sugita, Kohichi Takada, Masayoshi Kobune, Tadashi Hasegawa, Junji Kato

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 23 ( 5 ) 323 - 325 2017.05 [International journal]

Hepatitis C virus (HCV) reactivation is relatively rare compared with hepatitis B reactivation in patients treated with immunosuppressive or anticancer drugs. Here, we present the first case of genotype 2 HCV reactivation due to antiemetic steroid therapy during chemotherapy for hepatocellular carcinoma (HCC), which was verified by not only increased viral load but also pathological exacerbation of liver injury during HCV reactivation. Further chemotherapy for HCC could be continued without steroid therapy. This present case highlights the awareness of HCV reactivation and the management of complex situation.

DOI PubMed

A typical presentation of primary pulmonary epithelioid sarcoma misdiagnosed as non-small cell lung cancer.

Makoto Emori, Mitsuharu Tamakawa, Mitsunori Kaya, Kohichi Takada, Kazuyuki Murase, Chisa Fujita, Sayuri Sato, Ryuji Takahashi, Kanako C Hatanaka, Shintaro Sugita, Hiroshi Hirano, Toshihiko Yamashita, Tadashi Hasegawa

Pathology international 67 ( 4 ) 222 - 224 2017.04 [International journal]

DOI PubMed

Uterine epithelioid leiomyosarcoma with c-kit expression and YWHAE gene rearrangement: a case report of a diagnostic pitfall of uterine sarcoma.

Terufumi Kubo, Shintaro Sugita, Ryuichi Wada, Noriaki Kikuchi, Masahiro Iwasaki, Yumika Ito, Taro Sugawara, Hiromi Fujita, Makoto Emori, Ryoichi Tanaka, Hiroshi Hirano, Tsuyoshi Saito, Tadashi Hasegawa

Diagnostic pathology 12 ( 1 ) 26 - 26 2017.03 [International journal]

BACKGROUND: Uterine sarcoma is a rare tumor that is often difficult to classify based on morphological and immunohistochemical analysis alone. Limited access to molecular biological analysis in routine practice would hinder making a definitive diagnosis. CASE PRESENTATION: In this report, we describe a case of a mesenchymal tumor arising from the uterine cervix in a 52-year-old woman. From microscopic morphology of the resected specimen, epithelioid leiomyosarcoma, high-grade endometrial stromal sarcoma, or uterine gastrointestinal stromal tumor (GIST) were considered as differential diagnoses. The immunophenotype of the tumor featured smooth muscle differentiation and hormone receptor expression. The cell membrane and cytoplasm were positive for c-kit, although no mutation was found in the c-kit or PDGFRA gene. Fluorescence in situ hybridization (FISH) analysis revealed a relatively low frequency of YWHAE rearrangement, whereas there were few NUTM2A and NUTM2B split signals. CONCLUSIONS: In this case, the tumor was not typical of any three of the differential diagnoses mentioned above. However, insufficient frequency of YWHAE, NUTM2A, and NUTM2B gene rearrangement and absence of mutation in both the c-kit and PDGFRA genes suggested that this tumor should be categorized as epithelioid leiomyosarcoma. This is an instructive case showing a potential diagnostic pitfall of uterine sarcoma. Comprehensive approaches including molecular biological techniques are required for definitive diagnosis.

DOI PubMed

Influence of XRCC4 expression in esophageal cancer cells on the response to radiotherapy.

Masakazu Hori, Masanori Someya, Yoshihisa Matsumoto, Kensei Nakata, Mio Kitagawa, Tomokazu Hasegawa, Takaaki Tsuchiya, Yuki Fukushima, Toshio Gocho, Yasushi Sato, Hiroyuki Ohnuma, Junji Kato, Shintaro Sugita, Tadashi Hasegawa, Koh-Ichi Sakata

Medical molecular morphology 50 ( 1 ) 25 - 33 2017.03 [Domestic journal]

DNA double-strand break (DSB) is one of the most serious forms of damage induced by ionizing irradiation and is mainly repaired by the non-homologous end joining (NHEJ) repair. Immunohistochemical analysis of proteins involved in NHEJ, such as XRCC4 (X-ray repair cross-complementing protein 4), Ku86 and DNA-PKcs (DNA-dependent protein kinase, catalytic subunits), may be useful for predicting tumor radiosensitivity. We examined 92 patients with esophageal squamous cell carcinoma (ECSS) who were treated by radiotherapy between 1999 and 2008. Immunohistochemical examination of tumor tissue for Ki-67 and DSB-related proteins, including XRCC4, Ku86, and DNA-PKcs, was performed using pretreatment biopsy specimens. Low expression of XRCC4 was detected in 31 of 92 examined samples (33.7 %). The 5-year overall survival (OS) rate was 67.7 % in the low expression group and 31.0 % in the high expression group (P = 0.00). Multivariate analysis confirmed that advanced T-stage (HR 3.24, P = 0.01), radiation dose less than 66 Gy (HR 2.23, P = 0.02), absence of systemic chemotherapy (HR 2.59, P = 0.05), and high expression of XRCC4 (HR 12.0, P = 0.02) were independent prognostic factors for predicting poor OS. Other DSB-related proteins and Ki-67 were not predictive factors. XRCC4 expression might have an influence on results of radiotherapy for patients with ESCC.

DOI PubMed

Diagnosis of extraskeletal myxoid chondrosarcoma in the thigh using EWSR1-NR4A3 gene fusion: a case report.

Hiroki Kobayashi, Kazutaka Kikuta, Tetsuya Sekita, Michiro Susa, Kazumasa Nishimoto, Aya Sasaki, Kaori Kameyama, Shintaro Sugita, Tadashi Hasegawa, Masaya Nakamura, Morio Matsumoto, Hideo Morioka

Journal of medical case reports 10 ( 1 ) 321 - 321 2016.11 [International journal]

BACKGROUND: Extraskeletal myxoid chondrosarcoma is a rare soft tissue sarcoma that has unusual ultrastructural and molecular features. However, unlike other soft tissue sarcomas, it does not have specific clinical symptoms or radiological features, which can make its diagnosis difficult. Nevertheless, extraskeletal myxoid chondrosarcoma has a rare gene fusion (EWSR1-NR4A3) that is useful for making a differential diagnosis. CASE PRESENTATION: A 43-year-old Japanese man presented with a soft tissue mass in his right thigh. A physical examination and radiography revealed a large soft tissue mass. During magnetic resonance imaging, the mass exhibited isointensity on T1-weighted images and high intensity on T2-weighted images, as well as gadolinium enhancement at the side edge of the partition structure. Thus, we considered a possible diagnosis of a malignant myxoid soft tissue tumor, such as myxoid liposarcoma, myxofibrosarcoma, or metastatic carcinomas, including myoepithelial tumor and neuroendocrine tumor, and performed an incisional biopsy to make a definitive diagnosis. The pathological findings revealed a lobulated tumor with a myxoid structure and atypical spindle-shaped cells that created eosinophilic cord-like forms. Immunohistochemistry revealed that the tumor was positive for S-100 and negative for synaptophysin, chromogranin A, and pan keratin (AE1/AE3). The percentage of Ki-67 was 10 % in the hot spot area. Based on these clinicopathological findings, we initially considered the possibility of a myxoid liposarcoma, although we did not observe any lipoblasts. Therefore, we considered the possibility of an extraskeletal myxoid chondrosarcoma. As this tumor is very rare, we searched for the EWSR1-NR4A3 gene fusion using fluorescence in situ hybridization, which confirmed the diagnosis of extraskeletal myxoid chondrosarcoma. Positron emission tomography-computed tomography did not identify any obvious metastases, and we performed radical resection of our patient's vastus medialis and femur with a 3 cm margin. After the resection, we treated his resected femur using liquid nitrogen, and reconstructed his femur using autogenous fibula and plate fixation. No local recurrence or metastasis was observed at the 1-year follow-up. CONCLUSION: Genetic testing is useful for diagnosing extraskeletal myxoid chondrosarcoma based on the presence of the EWSR1-NR4A3 gene fusion.

PubMed

Pleomorphic Xanthoastrocytoma with Anaplastic Features in the Tectal Region in a Young Adult Patient: A Case Report.

Yuuto Suzuki, Yukinori Akiyama, Yuusuke Kimura, Shintaro Sugita, Tadashi Hasegawa, Nobuhiro Mikuni

World neurosurgery 94 580.e11-580.e15 2016.10 [International journal]

BACKGROUND: Pleomorphic xanthoastrocytomas (PXAs) in the tectal region are exceedingly rare and have distinctive clinicopathological features. CASE PRESENTATION: A 17-year-old man was admitted to our hospital owing to headache and diplopia. Magnetic resonance imaging showed a mass lesion in the tectal gland accompanied by obstructive hydrocephalus. A biopsy and third ventriculostomy were performed. Pathological examination revealed a PXA. Total excision of the lesion was achieved via an occipital transtentorial procedure performed 6 weeks after the biopsy. A pathological examination at that time showed a PXA with anaplastic features and a high mitotic index in surgical specimens. The patient's symptoms improved after the second operation, and radiation and temozolomide-based chemotherapy were administered. No recurrence was found at 24 months after the second operation. CONCLUSIONS: Maximum resections are recommended in cases with anaplastic features such as a high mitotic index in biopsy specimens because of the likelihood of recurrence and the low overall survival rate. We administered radiotherapy and temozolomide-based chemotherapy because of the high mitotic activity detected in surgical specimens. The postoperative course in this case is currently deemed acceptable.

DOI PubMed

Erdheim-Chester Disease Involving the Central Nervous System with the Unique Appearance of a Coated Vertebral Artery.

Hime Suzuki, Masahiko Wanibuchi, Katsuya Komatsu, Yukinori Akiyama, Takeshi Mikami, Shintaro Sugita, Tadashi Hasegawa, Mitsunori Kaya, Kohichi Takada, Nobuhiro Mikuni

NMC case report journal 3 ( 4 ) 125 - 128 2016.10 [Domestic journal]

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. It is characterized by multiple xanthogranulomatous masses throughout the body, predominantly in the tibia. One of the characteristic radiological findings of the lesions associated with ECD is a "coated artery," which is often observed in the aorta. Although approximately one-fourth of ECD cases involve the central nervous system (CNS), an intracranial-coated artery has only been reported in four cases. We report a case of ECD that involves the CNS and has the unique appearance of a coated vertebral artery (VA). These tumors entirely encase the bilateral VAs without stenosis and are attached to the dura. Cranial magnetic resonance imaging also showed multiple extra-axial tumors in the cavernous sinus, the frontal convexity, and the orbital cavity. Further investigation revealed additional extracranial lesions around the cervical carotid artery, at the bilateral tibia, and at the elbow joint. A biopsy of the cervical and tibial lesions confirmed ECD. Steroid therapy resulted in a month-long improvement of preoperative symptoms. However, the patient's condition gradually progressed and he died of pneumonia 1 year after ECD diagnosis. The encasement of the intracranial artery by the tumor without stenosis and the dural attachment suggest ECD, which requires whole body investigation.

DOI PubMed

Diagnostic utility of FOSB immunohistochemistry in pseudomyogenic hemangioendothelioma and its histological mimics.

Shintaro Sugita, Hiroshi Hirano, Noriaki Kikuchi, Terufumi Kubo, Hiroko Asanuma, Tomoyuki Aoyama, Makoto Emori, Tadashi Hasegawa

Diagnostic pathology 11 ( 1 ) 75 - 75 2016.08 [International journal]

Authorship： Lead author

BACKGROUND: Pseudomyogenic hemangioendothelioma (PHE) is an unusual vascular tumor of intermediate malignancy that rarely metastasizes and tends to arise in the lower limbs of young adults and children. Histologically, PHE shows fascicular proliferation of eosinophilic spindle cells and/or epithelioid cells showing "pseudomyogenic" morphology. Immunohistochemically, PHE is usually positive for vimentin, cytokeratin, CD31 and ERG. METHOD: We examined FOSB immunohistochemistry (IHC) in 27 cases consisting of 4 PHE and its histologic mimics including 6 epithelioid hemangioendotheliomas (EHE), 8 angiosarcomas (AS), 4 Kaposi sarcomas (KS) and 5 epithelioid sarcomas (ES). In addition, we performed IHC of CAMTA1 which has recently been established as a useful marker of EHE. We elucidated the diagnostic utility of FOSB IHC in the differential diagnosis of PHE and its histological mimics and also examined the usefulness of FOSB and CAMTA1 IHC combination in the differential diagnosis of the tumors. RESULTS: IHC revealed diffuse and strong FOSB expression in all PHE cases, while the other tumor types demonstrated limited, weak or no FOSB expression. All EHE cases exhibited diffuse and moderate to strong expression of CAMTA1. All tumor types except for EHE showed limited, weak or no CAMTA1 reactivity. CONCLUSIONS: Diffuse and strong FOSB expression was specific for PHE in the current series and FOSB IHC is an effective tool for differentiating between PHE and its histological mimics. Moreover, the combination of FOSB and CAMTA1 IHC is useful for distinguishing PHE from EHE.

DOI PubMed

[Treatment Outcomes of Adult-Onset Ewing Sarcoma: A Single-Center Retrospective Study of Five Cases].

Kazuyuki Murase, Kohichi Takada, Yusuke Kamihara, Makoto Usami, Masahiro Yoshida, Ayumi Tatekoshi, Akari Hashimoto, Yohei Arihara, Naotaka Hayasaka, Shogo Miura, Satoshi Iyama, Tsutomu Sato, Yasushi Sato, Koji Miyanishi, Masayoshi Kobune, Makoto Emori, Mitsunori Kaya, Toshihiko Yamashita, Shintaro Sugita, Tadashi Hasegawa, Junji Kato

Gan to kagaku ryoho. Cancer & chemotherapy 43 ( 8 ) 1015 - 8 2016.08 [Domestic journal]

UNLABELLED: We report the treatment outcomes of 5 cases of adult-onset Ewing sarcoma(ES)managed between 2011 and 2014. We examined prognostic factors including the primary lesion, tumor size, metastatic status, and serum LDH levels. RESULTS: The locations of the primary lesions included the limbs in 1 case and the trunk in 4; the cases in the trunk had a worse prognosis than that in the limbs. Tumor size was greater than 8 cm in only 1 patient, who also displayed evidence of metastases at presentation and high LDH levels. All the patients received chemotherapy consisting of alternating vincristine, doxorubicin, and cyclophosphamide(VDC)and etoposide and ifosfamide(IE). Surgery was selected for the treatment of 4 patients, and radiotherapy was administered to 1 patient for local treatment of the tumor. A median follow-up duration of 31.6 months revealed the 2-year overall survival rate and progression-free survival rate to be 80.0%. CONCLUSIONS: The prognosis of patients with adult-onset ES is poor; however, combined modality therapy, including VDC-IE, was demonstrated to improve the outcome of patients in the present study. Nevertheless, the patient with tumor size exceeding 8 cm, metastasis, and high LDH levels, relapsed 1 year after treatment, as reported previously. Further investigation is required to clarify the factors affecting prognosis in adults, and to develop effective therapies for patients with a poor prognosis.

PubMed

BAK is a predictive and prognostic biomarker for the therapeutic effect of docetaxel treatment in patients with advanced gastric cancer.

Tomohiro Kubo, Yutaka Kawano, Nobuaki Himuro, Shintaro Sugita, Yasushi Sato, Kazuma Ishikawa, Kohichi Takada, Kazuyuki Murase, Koji Miyanishi, Tsutomu Sato, Rishu Takimoto, Masayoshi Kobune, Takayuki Nobuoka, Koichi Hirata, Tetsuji Takayama, Mitsuru Mori, Tadashi Hasegawa, Junji Kato

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 19 ( 3 ) 827 - 38 2016.07 [Domestic journal]

BACKGROUND: Preoperative chemotherapy is a promising strategy for downstaging advanced gastric cancer before radical resection, although severe adverse events can occur and clinical outcomes are often unsatisfactory. To identify predictive biomarkers of drug sensitivity, we used a well-designed functional apoptosis assay and assessed the correlations between chemosensitivity and clinical outcomes. METHODS: Drug sensitivity to docetaxel, cisplatin, and 5-fluorouracil was examined in 11 gastric cancer cell lines. BCL2-homology domain 3 (BH3) profiling was performed and assessed for correlations with drug sensitivity. Immunohistochemical staining of clinical gastric cancer specimens was performed before preoperative chemotherapy, and correlations with histopathological responses and clinical outcomes were assessed. RESULTS: BIM (BCL2L11)-BH3 profiling results correlated with docetaxel sensitivity and BAK protein expression, whose knockdown caused docetaxel resistance. The BAK expression indexes of 69 gastric cancer specimens before preoperative chemotherapy (including docetaxel treatment) were determined by multiplying numerical values describing the degrees of BAK positivity and staining intensity observed. Patients whose specimens showed good chemotherapeutic histopathological responses had higher BAK indexes than those with poor responses. Patients with BAK index values ≥3 showed improved progression-free survival (HR, 2.664; 95 % CI, 1.352-5.248; P = 0.005) and overall survival (HR, 3.390; 95 % CI, 1.549-7.422; P = 0.002). CONCLUSIONS: BH3 profiling clearly showed that BIM expression, which depends on BAK expression, correlated with docetaxel sensitivity. BAK expression in gastric cancer is thus predictive of chemotherapeutic responses to docetaxel and clinical prognosis in patients treated with preoperative chemotherapy.

DOI PubMed

DNA methyltransferase-3 like protein expression in various histological types of testicular germ cell tumor.

Taeko Matsuoka, Koji Kawai, Satoshi Ando, Shintaro Sugita, Shuya Kandori, Takahiro Kojima, Jun Miyazaki, Hiroyuki Nishiyama

Japanese journal of clinical oncology 46 ( 5 ) 475 - 81 2016.05 [International journal]

OBJECTIVE: DNA methyltransferase 3-like plays an important role in germ cell development. The aim of this study was to analyse the DNA methyltransferase 3-like protein expression in testicular germ cell tumors. METHODS: The immunohistochemical expression of DNA methyltransferase 3-like was examined in 86 testicular germ cell tumor specimens in various clinical settings. The association between DNA methyltransferase 3-like expression and disease stage was analyzed. RESULTS: DNA methyltransferase 3-like was strongly expressed in seven of the eight pure embryonal carcinomas (87.5%). Partial DNA methyltransferase 3-like expression was observed in 6 of 23 (26.1%) pure seminomas. Various degrees of DNA methyltransferase 3-like expression was observed in all four pure yolk sac tumors, of which three were prepubertal yolk sac tumors. In mixed germ cell tumors, DNA methyltransferase 3-like protein was expressed in various degrees in elements of the embryonal carcinoma (14/18, 77.8%), seminoma (4/11, 36.4%), teratoma (4/7, 57.1%) and choriocarcinoma (3/3, 100%) but not in the yolk sac tumors (0/4). When DNA methyltransferase 3-like expression was analyzed according to disease stages, it was significantly correlated with advanced seminoma rather than Stage I seminoma (46.2 vs. 0%, P = 0.019), whereas there was no significant difference in the DNA methyltransferase 3-like-positive proportion between Stage I and advanced disease in the mixed germ cell tumors. CONCLUSIONS: Our findings suggest that DNA methyltransferase 3-like protein may play roles not only in the development of embryonal carcinoma but also in the development of advanced pure seminoma and pure yolk sac tumor.

DOI PubMed

Diagnosis of desmoplastic small-round-cell tumor by cytogenetic analysis: a case report.

Senn Wakahashi, Tamotsu Sudo, Kotaro Ichida, Shintaro Sugita, Tadashi Hasegawa, Shoji Nagao, Satoshi Yamaguchi, Toshiko Sakuma, Hideto Yamada

Clinical case reports 4 ( 5 ) 520 - 3 2016.05 [International journal]

DOI PubMed

Diagnostic use of fluorescence in situ hybridization in expert review in a phase 2 study of trabectedin monotherapy in patients with advanced, translocation-related sarcoma.

Shintaro Sugita, Hiroko Asanuma, Tadashi Hasegawa

Diagnostic pathology 11 37 - 37 2016.04 [International journal]

Authorship： Lead author , Corresponding author

BACKGROUND: Fluorescence in situ hybridization (FISH) is one of the most powerful genetic analysis tools for pathological diagnoses. FISH can detect various genetic abnormalities including gene translocation that was specifically found in translocation-related sarcomas (TRSs). Here, we report the use of FISH in expert review in a phase 2 study of trabectedin monotherapy for patients with advanced TRS. METHODS: TRS patients (n = 76) were enrolled in the trial at 12 study sites after pathological diagnoses were made, including morphological examination with or without evidence of translocation by genetic testing. Following histological reviews of the representative specimens at the study sites, we performed immunohistochemistry using the appropriate antibodies and FISH for genetic confirmation of the tumor types in the expert review. RESULTS: Among the 76 TRS cases, no split signal for SS18 probe was detected by FISH in three synovial sarcoma cases that were diagnosed at the study sites. Malignant peripheral nerve sheath tumor (MPNST) was diagnosed in two cases and sarcomatoid carcinoma in one. One of the cases was a small round cell variant of MPNST. After excluding these three cases, we assessed the other 73. There were no split signals detected in 7 of the 73 cases by FISH analysis, due to decalcification and hyperfixation procedures. Excluding these seven cases, FISH detected translocations in 95 % (63/66) of the study cases with a high sensitivity. CONCLUSIONS: The diagnosis of TRS by FISH was highly sensitive and enabled genetic confirmation of the pathological diagnoses. We strongly recommend FISH as a confirmatory diagnostic test for TRS, which would enable the selection of patients with TRS in whom trabectedin is expected to be effective. This study was done in part that registered with Japan Pharmaceutical Information Center, number JapicCTI-121850.

DOI PubMed

Primary pulmonary Ewing sarcoma.

Hiroshi Hirano, Hajime Maeda, Yukiyasu Takeuchi, Naoko Ose, Hiromi Fujita, Shintaro Sugita, Tadashi Hasegawa

Pathology international 66 ( 4 ) 239 - 41 2016.04 [International journal]

DOI PubMed

Angiomyxomatous tumor of the falx cerebri.

Shintaro Sugita, Masahiko Obata, Seiji Takebayashi, Tomoki Kikuchi, Tadashi Hasegawa

Pathology international 66 ( 1 ) 50 - 1 2016.01 [International journal]

Authorship： Lead author

DOI PubMed

Surgical and oncological impact of main pancreatic duct spread in invasive ductal adenocarcinoma: A clinicopathological study of 184 resected cases

Masayuki Ishii, Yasutoshi Kimura, Shintaro Sugita, Masafumi Imamura, Tatsuya Ito, Takayuki Nobuoka, Makoto Meguro, Tadashi Hasegawa, Toru Mizuguchi, Koichi Hirata

Pancreatology ( Elsevier BV ) 15 ( 6 ) 681 - 687 2015.11 [Refereed]

DOI

IgG4-related disease initially presented as an orbital mass lesion mimicking optic nerve sheath meningioma.

Shouhei Noshiro, Masahiko Wanibuchi, Yukinori Akiyama, Satoshi Okawa, Shunya Ohtaki, Toshiya Sugino, Satoshi Iihoshi, Takeshi Mikami, Shintaro Sugita, Tadashi Hasegawa, Nobuhiro Mikuni

Brain tumor pathology 32 ( 4 ) 286 - 90 2015.10 [Domestic journal]

We report a case of an optic nerve mass lesion associated with IgG4-related disease. A 39-year-old man presented with right blurred vision and proptosis 8 years before admission. Magnetic resonance imaging showed a mass lesion in the center of the right orbit, which was diagnosed as optic nerve sheath meningioma by neuroradiologists and neurosurgeons. Irradiation was selected for treatment of the lesion on the basis of the radiological diagnosis; subsequently, the lesion gradually reduced in size. However, regrowth of an optic nerve mass lesion observed during the previous 2 years caused remarkable exophthalmos, and removal of the orbital mass lesion was performed via a transcranial orbital approach. Pathological examinations resulted in a diagnosis of IgG4-related disease, and hematological tests revealed an elevated level of serum IgG4. Additional radiological examinations showed mass lesions in the left maxillary nerve, bilateral inferior alveolar nerves, paravertebral tissue, and left kidney. Treatment with oral steroids has produced a reduction in the size of these lesions.

DOI PubMed

Nasopharyngeal hyalinizing clear cell carcinoma with EWSR1 rearrangements diagnosed by fluorescence in situ hybridization.

Atsushi Fukuda, Yohei Tagami, Akira Takasawa, Shintaro Sugita, Rinnosuke Kuramoto, Suguru Imai, Tadashi Hasegawa, Keiji Iizuka

Auris, nasus, larynx 42 ( 5 ) 412 - 5 2015.10 [International journal]

Hyalinizing clear cell carcinoma (HCCC) is a rare, low-grade salivary gland neoplasm with a predilection for the palate and tongue. A 63-year-old woman presented a 14×14×17-mm mass at the roof of the nasopharynx. Endoscopic resection was performed via a transnasal approach. Histopathological findings of the salivary gland tumor indicated hyalinization of the stroma and neoplastic cells with clear cytoplasm without mucin. Fluorescence in situ hybridization analysis revealed that the tumor cells were positive for EWSR1 rearrangement. We finally diagnosed this case as HCCC of the nasopharynx. EWSR1 rearrangements are non-existent in other salivary gland tumors with clear cell change; thus, the identification of this rearrangement was very useful in accurately diagnosing HCCC.

DOI PubMed

Experience using denosumab for lung metastases of giant cell tumor of bone

Yuto Watanabe, Mitsunori Kaya, Mikito Sasaki, Masato Emori, Yasutaka Murahashi, Emi Mizushima, Tamotsu Souma, Shintaro Sugita, Tadashi Hasegawa, Toshihiko Yamashita

European Orthopaedics and Traumatology ( Springer Verlag ) 6 ( 3 ) 239 - 241 2015.09

The treatment of unresectable multiple lung metastasis of giant cell tumor of bone (GCTB) is challenging. In the current manuscript, we present a case who presented with multiple lung metastases of GCTB and was successfully managed with the use of denosumab allowing for surgical resection of the metastatic lesions that was previously deemed unresectable. Pathologic examination also clearly demonstrated the histological effects of denosumab. We emphasize on effective response to denosumab even in metastatic GCTB.

DOI

Prognostic impact of CD109 expression in myxofibrosarcoma.

Makoto Emori, Tomohide Tsukahara, Kenji Murata, Shintaro Sugita, Tomoko Sonoda, Mitsunori Kaya, Tamotsu Soma, Mikito Sasaki, Satoshi Nagoya, Tadashi Hasegawa, Takuro Wada, Noriyuki Sato, Toshihiko Yamashita

Journal of surgical oncology 111 ( 8 ) 975 - 9 2015.06 [International journal]

BACKGROUND: CD109, a TGF-β co-receptor, is reported to be preferentially expressed during the early stages of tumorigenesis in several carcinoma types. Myxofibrosarcoma is one of the most common soft-tissue sarcomas found in elderly patients. This study aimed to elucidate the impact of CD109 expression in myxofibrosarcoma on prognosis and recurrence. METHODS: Immunohistochemical staining for CD109 was performed on archival specimens from 37 patients. The Fisher exact test was used to evaluate association between CD109 expression and other clinicopathological features. Survival analysis was performed using Kaplan-Meier curves, and the prognostic significance was evaluated using the log-rank test. Multivariate analysis of factors was performed using Cox regression analysis. RESULTS: CD109 overexpression was significantly associated with surgical stage and distant metastasis (P = 0.00499, and 0.011, respectively). The frequency of CD109 overexpression was approximately 10% and CD109 overexpression was significantly associated with decreased overall survival (P = 0.004). Five-year overall survival rates 77% and 0% for CD109-negative and CD109-positive patients, respectively. In multivariate analysis, CD109 overexpression was the only independent risk factor for poor outcome (P = 0.02; hazard ratio, 10.64; 95% confidence interval, 1.47-76.91). CONCLUSIONS: Immunohistochemical CD109 expression in myxofibrosarcoma was associated with poor prognosis.

DOI PubMed

Recurrent pulmonary synovial sarcoma effectively treated with amrubicin: A case report.

Hiroaki Satoh, Norio Takayashiki, Toshihiro Shiozawa, Kunihiko Miyazaki, Gen Ohara, Katsunori Kagohashi, Koichi Kurishima, Shintaro Sugita, Tomoyuki Aoyama, Tadashi Hasegawa, Nobuyuki Hizawa

Experimental and therapeutic medicine 9 ( 5 ) 1947 - 1949 2015.05 [International journal]

Pulmonary synovial sarcoma is a rare but aggressive disease. The present study describes the case of a 68-year-old female with pulmonary synovial sarcoma. The patient was mistakenly treated for small cell lung cancer due to false-positive staining for synaptophysin and cluster of differentiation 56. Despite severe myelotoxicity, platinum-containing chemotherapies (cisplatin plus irinotecan and carboplatin plus etoposide) were not effective. As a third-line therapy, the patient received amrubicin (AMR) monotherapy. A partial response was achieved, and the patient was able to undertake ordinary daily life at home for 13 months from the initiation of AMR chemotherapy. Due to the atypical clinical condition and unusual response to chemotherapy in this patient, the pathological examination was repeated. The SS18 split-signal was detected in fluorescence in situ hybridization analysis. From these results, the tumor was diagnosed as a monophasic synovial sarcoma. To the best of our knowledge, this is the first case of a patient with pulmonary synovial sarcoma who underwent successful treatment with AMR. The present case could demonstrate a specific chemosensitivity of such a rare tumor.

PubMed

A novel CIC-FOXO4 gene fusion in undifferentiated small round cell sarcoma: a genetically distinct variant of Ewing-like sarcoma.

Shintaro Sugita, Yasuhito Arai, Akiko Tonooka, Natsuko Hama, Yasushi Totoki, Tomoki Fujii, Tomoyuki Aoyama, Hiroko Asanuma, Tomohide Tsukahara, Mitsunori Kaya, Tatsuhiro Shibata, Tadashi Hasegawa

The American journal of surgical pathology 38 ( 11 ) 1571 - 6 2014.11 [International journal]

Authorship： Lead author

Differential diagnosis of small round cell sarcomas (SRCSs) grouped under the Ewing sarcoma family of tumors (ESFT) can be a challenging situation for pathologists. Recent studies have revealed that some groups of Ewing-like sarcoma show typical ESFT morphology but lack any EWSR1-ETS gene fusions. Here we identified a novel gene fusion, CIC-FOXO4, in a case of Ewing-like sarcoma with a t(X;19)(q13;q13.3) translocation. The patient was a 63-year-old man who had an asymptomatic, 30-mm, well-demarcated, intramuscular mass in his right posterior neck, and imaging findings suggested a diagnosis of high-grade sarcoma. He was treated with complete resection and subsequent radiotherapy and chemotherapy. He was alive without local recurrence or distant metastasis 6 months after the operation. Histologic examination revealed SRCS with abundant desmoplastic fibrous stroma suggesting a desmoplastic small round cell tumor. Immunohistochemical analysis showed weak to moderate and partial staining for MIC2 (CD99) and WT1, respectively. High-throughput transcriptome sequencing revealed a gene fusion, and the genomic rearrangement between the CIC and FOXO4 genes was identified by fluorescence in situ hybridization. Aside from the desmoplastic stroma, the CIC-FOXO4 fusion sarcoma showed morphologic and immunohistochemical similarity to ESFT and Ewing-like sarcomas, including the recently described CIC-DUX4 fusion sarcoma. Although clinicopathologic analysis with additional cases is necessary, we conclude that CIC-FOXO4 fusion sarcoma is a new type of Ewing-like sarcoma that has a specific genetic signature. These findings have important implications for the differential diagnosis of SRCS.

DOI PubMed

Expression of the oncoprotein gankyrin and phosphorylated retinoblastoma protein in human testis and testicular germ cell tumor.

Satoshi Ando, Taeko Matsuoka, Koji Kawai, Shintaro Sugita, Akira Joraku, Takahiro Kojima, Takahiro Suetomi, Jun Miyazaki, Jun Fujita, Hiroyuki Nishiyama

International journal of urology : official journal of the Japanese Urological Association 21 ( 10 ) 992 - 8 2014.10 [International journal]

OBJECTIVE: The oncoprotein, gankyrin, is known to facilitate cell proliferation through phosphorylation and degradation of retinoblastoma protein. In the present study, we evaluated the expression of gankyrin and phosphorylated retinoblastoma protein in human testis and testicular germ cell tumors. METHODS: The effects of suppression of gankyrin by locked nucleic acid on phosphorylation status of retinoblastoma and cell proliferation were analyzed using western blot analysis and testicular tumor cell line NEC8. The expressions of gankyrin, retinoblastoma and retinoblastoma protein were analyzed in 93 testicular germ cell tumor samples and five normal human testis by immunohistochemistry. The retinoblastoma protein expression was determined using an antibody to retinoblastoma protein, Ser795. RESULTS: Gankyrin was expressed in NEC8 cells as well as a normal human testis and testicular tumors. Suppression of gankyrin by locked nucleic acid led to suppression of retinoblastoma protein and cell proliferation in NEC8 cells. Immunohistochemistry of normal testis showed that gankyrin is expressed dominantly in spermatocytes. In testicular germ cell tumors, high expressions of gankyrin and phosphorylated-retinoblastoma protein were observed in seminoma and embryonal carcinoma, whereas the expressions of both proteins were weak in histological subtypes of non-seminoma. Growing teratoma and testicular malignant transformation tissues expressed phosphorylated-retinoblastoma protein strongly, but gankyrin faintly. CONCLUSION: Gankyrin is dominantly expressed in normal spermatocytes and seminoma/embryonal carcinoma, and its expression correlates well with retinoblastoma protein expression except in the growing teratoma and testicular malignant transformation cases. These data provide new insights into the molecular mechanisms of normal spermatogenesis and pathogenesis of testicular germ cell tumors.

DOI PubMed

Diagnostic utility of NCOA2 fluorescence in situ hybridization and Stat6 immunohistochemistry staining for soft tissue angiofibroma and morphologically similar fibrovascular tumors.

Shintaro Sugita, Tomoyuki Aoyama, Kei Kondo, Yoshiko Keira, Jiro Ogino, Katsuya Nakanishi, Mitsunori Kaya, Makoto Emori, Tomohide Tsukahara, Hisaya Nakajima, Masayuki Takagi, Tadashi Hasegawa

Human pathology 45 ( 8 ) 1588 - 96 2014.08 [International journal]

Authorship： Lead author

Soft tissue angiofibroma (STA), a recently suggested new histologic entity, is a benign fibrovascular soft tissue tumor composed of bland spindle-shaped tumor cells with abundant collagenous to myxoid stroma and branching small vessels. The lesion has a characteristic AHRR-NCOA2 fusion gene derived from chromosomal translocation of t(5;8)(p15;q13). However, morphologically similar tumors containing abundant fibrovascular and myxoid stroma can complicate diagnosis. We designed an original DNA probe for detecting NCOA2 split signals on fluorescence in situ hybridization (FISH) and estimated its utility with 20 fibrovascular tumors: 4 each of STAs, solitary fibrous tumors (SFTs), and cellular angiofibromas and 3 each of low-grade myxofibrosarcomas, myxoid liposarcomas, and low-grade fibromyxoid sarcomas. We also performed FISH for 13q14 deletion and immunohistochemistry (IHC) staining for estrogen receptor, progesterone receptor, retinoblastoma protein, and MUC-4 expression. Furthermore, IHC for Stat6 was conducted in the 20 cases analyzed by FISH and in an additional 26 SFTs. We found moderate to strong nuclear Stat6 expression in all SFTs but no expression in the other tumors. Both estrogen receptor and progesterone receptor expressions were observed in STAs, SFTs, and cellular angiofibromas. Expression of retinoblastoma protein was found in less than 10% of cells in all tumor types except myxoid liposarcoma. The low-grade fibromyxoid sarcomas were strongly positive for MUC-4. All STAs showed NCOA2 split signals on FISH. All tumors, regardless of histologic type, had 13q14 deletion. The NCOA2 FISH technique is a practical method for confirming STA diagnosis. The combination of NCOA2 FISH and Stat6 IHC proved effective for the differential diagnosis of STA, even when using small biopsy specimens.

DOI PubMed

Analysis of gene expression profiles of soft tissue sarcoma using a combination of knowledge-based filtering with integration of multiple statistics.

Anna Takahashi, Robert Nakayama, Nanako Ishibashi, Ayano Doi, Risa Ichinohe, Yoriko Ikuyo, Teruyoshi Takahashi, Shigetaka Marui, Koji Yasuhara, Tetsuro Nakamura, Shintaro Sugita, Hiromi Sakamoto, Teruhiko Yoshida, Tadashi Hasegawa, Hiro Takahashi

PloS one 9 ( 9 ) e106801 2014 [International journal]

The diagnosis and treatment of soft tissue sarcomas (STS) have been difficult. Of the diverse histological subtypes, undifferentiated pleomorphic sarcoma (UPS) is particularly difficult to diagnose accurately, and its classification per se is still controversial. Recent advances in genomic technologies provide an excellent way to address such problems. However, it is often difficult, if not impossible, to identify definitive disease-associated genes using genome-wide analysis alone, primarily because of multiple testing problems. In the present study, we analyzed microarray data from 88 STS patients using a combination method that used knowledge-based filtering and a simulation based on the integration of multiple statistics to reduce multiple testing problems. We identified 25 genes, including hypoxia-related genes (e.g., MIF, SCD1, P4HA1, ENO1, and STAT1) and cell cycle- and DNA repair-related genes (e.g., TACC3, PRDX1, PRKDC, and H2AFY). These genes showed significant differential expression among histological subtypes, including UPS, and showed associations with overall survival. STAT1 showed a strong association with overall survival in UPS patients (logrank p = 1.84 × 10(-6) and adjusted p value 2.99 × 10(-3) after the permutation test). According to the literature, the 25 genes selected are useful not only as markers of differential diagnosis but also as prognostic/predictive markers and/or therapeutic targets for STS. Our combination method can identify genes that are potential prognostic/predictive factors and/or therapeutic targets in STS and possibly in other cancers. These disease-associated genes deserve further preclinical and clinical validation.

DOI PubMed

[Case of metastatic malignant melanoma of the urinary bladder].

Atsushi Ikeda, Tomoaki Miyagawa, Masahiro Kurobe, Masahiro Uchida, Takahiro Kojima, Masakazu Tsutsumi, Shusaku Ito, Shintaro Sugita, Hiroyuki Nishiyama

Hinyokika kiyo. Acta urologica Japonica 59 ( 9 ) 579 - 82 2013.09 [Domestic journal]

A 54-year-old woman underwent resection of malignant melanoma of the left leg and inguinal lymph node metastases and subsequent radiation therapy (60 Gy) following three courses of dacarbazine, nimustine, vincristine and interferon-beta chemotherapy in January 2010. In September 2011, she was referred to our department with the chief complaint of asymptomatic gross hematuria. A non-papillary bladder tumor was detected on cystoscopy and fluorodeoxyglucose (FDG) positron emission fomography-computed tomography revealed increased uptake of FDG only in the area of the bladder tumor. Melanoma cells were also found on urinary cytology. Our diagnosis was metastatic malignant melanoma of the bladder. Complete transurethral resection of the bladder tumor was performed, and pathological examination confirmed metastatic malignant melanoma. Metastatic bladder tumors constitute less than 5% of all bladder tumors. There are metastases in other organs at the time of diagnosis in almost all cases. In Japan, metastatic malignant melanoma of the urinary bladder is rare in clinical practice, there having been about a dozen reported cases. Solitary metastasis as in our case is even rarer.

PubMed

Macrophage migration inhibitory factor and stearoyl-CoA desaturase 1: potential prognostic markers for soft tissue sarcomas based on bioinformatics analyses.

Hiro Takahashi, Robert Nakayama, Shuhei Hayashi, Takeshi Nemoto, Yasuyuki Murase, Koji Nomura, Teruyoshi Takahashi, Kenji Kubo, Shigetaka Marui, Koji Yasuhara, Tetsuro Nakamura, Takuya Sueo, Anna Takahashi, Kaname Tsutsumiuchi, Tsutomu Ohta, Akira Kawai, Shintaro Sugita, Shinjiro Yamamoto, Takeshi Kobayashi, Hiroyuki Honda, Teruhiko Yoshida, Tadashi Hasegawa

PloS one 8 ( 10 ) e78250 2013 [International journal]

The diagnosis and treatment of soft tissue sarcomas (STSs) has been particularly difficult, because STSs are a group of highly heterogeneous tumors in terms of histopathology, histological grade, and primary site. Recent advances in genome technologies have provided an excellent opportunity to determine the complete biological characteristics of neoplastic tissues, resulting in improved diagnosis, treatment selection, and investigation of therapeutic targets. We had previously developed a novel bioinformatics method for marker gene selection and applied this method to gene expression data from STS patients. This previous analysis revealed that the extracted gene combination of macrophage migration inhibitory factor (MIF) and stearoyl-CoA desaturase 1 (SCD1) is an effective diagnostic marker to discriminate between subtypes of STSs with highly different outcomes. In the present study, we hypothesize that the combination of MIF and SCD1 is also a prognostic marker for the overall outcome of STSs. To prove this hypothesis, we first analyzed microarray data from 88 STS patients and their outcomes. Our results show that the survival rates for MIF- and SCD1-positive groups were lower than those for negative groups, and the p values of the log-rank test are 0.0146 and 0.00606, respectively. In addition, survival rates are more significantly different (p = 0.000116) between groups that are double-positive and double-negative for MIF and SCD1. Furthermore, in vitro cell growth inhibition experiments by MIF and SCD1 inhibitors support the hypothesis. These results suggest that the gene set is useful as a prognostic marker associated with tumor progression.

DOI PubMed

[Mixed type ureteral endometriosis : a case report and a review of the Japanese literature].

Masahiro Kurobe, Takahiro Kojima, Masahiro Uchida, Tomoaki Miyagawa, Masakazu Tsutsumi, Shintaro Sugita

Hinyokika kiyo. Acta urologica Japonica 58 ( 7 ) 329 - 33 2012.07 [Domestic journal]

Ureteral endometriosis is a rare but important clinical problem that requires early detection and treatment. The urinary tract is affected in approximately 2% of women with endometriosis. Even though the bladder is the most frequent urinary tract organ affected in these patients,the ureter is also affected in 10-40% of the cases, thus requiring immediate clinical attention. The majority of endometrial lesions is typically located in the lower segment of the ureter and is often difficult to differentiate between endometriosis and malignancy. Ureteral endmetriosis should be considered for women with hydronephrosis. In this report we present one clinical case of mixed-type ureteral endometriosis. A 37-year-old woman was referred to our hospital due to left hydronephrosis. Contrast-enhanced CT scan confirmed left hydronephrosis and also showed a solid mass at the left lower ureter. Retrograde pyelography revealed stenosis of the left lower ureter and Renogram revealed severely impaired renal function. Laparoscopic nephroureterectomy was performed. Pathologically, mixed-type endometriosis of the left ureter was diagnosed.

PubMed

[Spindle cell sarcoma of the penis: a case report].

Tomokazu Kimura, Takehiro Oikawa, Atsushi Ikeda, Takayuki Yoshino, Takahiro Suetomi, Jun Miyazaki, Toru Shimazui, Takayuki Hashimoto, Shintaro Sugita, Masayuki Noguchi, Hiroyuki Nishiyama

Hinyokika kiyo. Acta urologica Japonica 58 ( 6 ) 299 - 305 2012.06 [Domestic journal]

A 75-year-old man, with a past history of radiation therapy for prostatic carcinoma ten years ago, was referred to our hospital with complaints of penile tumor. After pathological examination by core biopsy, the patient was treated by radical penectomy for a penile tumor. Pathological examinations demonstrated that the tumor was composed of pleomorphic spindle cells without any differentiation tendency and diagnosed as spindle cell sarcoma. Although the patient had a past history of radiation therapy for the prostate, the causal relation of development of penile sarcoma with the radiation therapy was uncertain because the main tumor was very near but outside of the irradiation field. The sarcoma rarely occurs in the penis, and this is the first report of penile spindle cell sarcoma, to our knowledge.

PubMed

Extra-abdominal desmoid tumor in the subcutis of the thigh.

Yasuhiro Fujisawa, Shintaro Sugita, Yasuhiro Kawachi, Fujio Otsuka

The Journal of dermatology 38 ( 8 ) 810 - 2 2011.08 [International journal]

DOI PubMed

Congenital-idiopathic superficial femoral artery aneurysm in a 7-year-old child.

Muneaki Matsubara, Yuji Hiramatsu, Shintaro Sugita, Naotaka Atsumi, Masatsugu Terada, Yuzuru Sakakibara

Journal of vascular surgery 53 ( 6 ) 1699 - 701 2011.06 [International journal]

Superficial femoral artery aneurysm in children is distinctly uncommon, and usually results from infection, vasculitis, connective tissue disorder, or trauma. We report a 7-year-old girl who had multiple fusiform aneurysms of the right superficial femoral artery, with no evidence of related disorders. The patient successfully underwent aneurysm resection and femoral artery reconstruction with autogenous saphenous vein. Histologic examination revealed intimal thickening with fibroplasia without severe inflammatory infiltrates or cystic medial necrosis, suggesting a congenital-idiopathic arterial aneurysm. Three years after the procedure, the saphenous vein graft is fully patent and the patient is in good condition.

DOI PubMed

IGFBP-1 is expressed specifically in ovarian clear cell adenocarcinoma.

Shintaro Sugita, Yukio Morishita, Junko Kano, Shuichiro Furuya, Aya Shiba-Ishii, Masayuki Noguchi

Histopathology 58 ( 5 ) 729 - 38 2011.04 [International journal]

Authorship： Lead author

AIMS: To investigate the specific expression of insulin-like growth factor binding protein-1 (IGFBP-1) in ovarian clear cell adenocarcinoma (CCA). METHODS AND RESULTS: Immunohistochemistry and in situ hybridization for IGFBP-1 were performed in normal endometrium, placenta, and 100 surgically resected cases of ovarian cancer including 31 CCAs and 69 non-CCAs. Immunohistochemistry for hepatocyte nuclear factor-1 (HNF-1β) was also examined in all cases. Specific expression of IGFBP-1 was confirmed in secretory endometrium, decidua of placenta and Arias-Stella glands of miscarriage material. Among ovarian cancers, almost all cases of CCA showed expression of both IGFBP-1 protein and mRNA, but non-CCA hardly expressed IGFBP-1. There was a significant difference between CCA and non-CCA in the expression of IGFBP-1 protein and mRNA. No correlation was found between the rate of IGFBP-1 expression and pathological T and N factors of the tumour-node-metastasis (TNM) classification. All CCA cases except for one exhibited expression of HNF-1β protein, whereas only 15.9% of non-CCAs did so. CONCLUSION: The expression of IGFBP-1 in CCA is more specific than that of HNF-1β. IGFBP-1 shows expression by decidual endometrium and Arias-Stella glands, and CCA also exhibits characteristic expression. These results indicate that IGFBP-1 is a immunohistochemical marker for CCA.

DOI PubMed

Thunderclap headache without hypertension in a patient with pheochromocytoma.

Masahiko Watanabe, Akimitsu Takahashi, Hitoshi Shimano, Hisato Hara, Shintaro Sugita, Kiyotaka Nakamagoe, Akira Tamaoka

The journal of headache and pain 11 ( 5 ) 441 - 4 2010.10 [International journal]

Pheochromocytoma is a well known, catecholamine-producing tumor characterized by hypertension, headache, hyperglycemia, hypermetabolism, and hyperhydrosis. Approximately 65% of cases of pheochromocytoma were shown to be associated with hypertension. A case of pheochromocytoma that presented with thunderclap headache (TCH) and palpitations is reported. The patient never showed hypertension during the course of the disease. Paroxysmal headache and palpitations led to the identification of the underlying condition, and the final diagnosis was confirmed by histopathological examination of a surgical specimen. Pheochromocytoma should be identified as a less common although important cause of TCH. In addition, due to its lack of utility in identifying this disorder, negative cranial imaging may impede further investigation of extracranial lesions that may be the cause of a patient's headache. According to the International Classification of Headache Disorders (ICHD)-II, headache attributed to pheochromocytoma usually develops concomitantly with an abrupt increase in blood pressure. In our case, however, hypertension was never observed, even when the patient was symptomatic. This is the first report of a case of pheochromocytoma with TCH without hypertension.

DOI PubMed

Analysis of CHOP rearrangement in pleomorphic liposarcomas using fluorescence in situ hybridization.

Shintaro Sugita, Kunihiko Seki, Karin Yokozawa, Naobumi Tochigi, Koh Furuta, Masanori Hisaoka, Hiroshi Hashimoto, Tadakazu Shimoda, Tadashi Hasegawa

Cancer science 100 ( 1 ) 82 - 7 2009.01 [International journal]

Authorship： Lead author

Pleomorphic liposarcoma (PLS) is an aggressive subtype of liposarcoma composed of high-grade sarcoma with pleomorphic lipoblasts. PLS usually exhibits a heterogeneous histology and sometimes has a myxoid or round cell area similar to myxoid/round cell liposarcomas (MLS/RCs). Using fluorescence in situ hybridization (FISH) analysis, we investigated the existence of CHOP split signals in various histological areas of PLS including the MLS/RC-like feature and also estimated the distribution of various signals with polyploidy and amplification. Moreover, to detect CHOP fusion transcripts we performed nested reverse transcription-polymerase chain reaction (RT-PCR). Seven PLSs and three MLS/RCs were selected for FISH analysis using the locus-specific indicator CHOP (12q13) dual color, break apart probe (Vysis, USA). The FISH analysis was applied to formalin-fixed, paraffin-embedded tissue sections of representative areas in all cases. Six of seven PLS cases showed the CHOP split signal ranging from 0.5% to 3% of counted nuclei, while all cases of MLS/RC exhibited CHOP rearrangement in more than 50% of counted nuclei. All cases of PLS showed a varied distribution of extra signals with polyploidy and amplification in each histological area. No CHOP fusion transcript was found in any case of PLS by nested RT-PCR. A CHOP rearrangement in PLS should be recognized only as a representative part of complex karyotypes, because the number of cells with split signals was minute compared with that of MLS/RC, and the signals were found in any area despite their histological differences. The cytogenetic background of PLS and that of MLS/RC are obviously different despite histological similarity.

DOI PubMed

Gastric T-cell lymphoma with cytotoxic phenotype.

Shintaro Sugita, Tatsuo Iijima, Shuichiro Furuya, Junko Kano, Akinori Yanaka, Keiichiro Ohta, Hiroshi Kojima, Masayuki Noguchi

Pathology international 57 ( 2 ) 108 - 14 2007.02 [International journal]

Authorship： Lead author

Primary gastric lymphoma usually originates from B cells of mucosa-associated lymphoid tissue (MALT) infected with Helicobacter pylori. When T-cell lymphomas develop in the stomach, they usually occur in association with infection by human T-lymphotropic virus type 1 and gastric involvement of adult T-cell leukemia. Reported herein is a unique and informative case of gastric peripheral T-cell lymphoma with a cytotoxic phenotype that histologically mimicked, and had to be carefully distinguished from, MALT-type B-cell lymphoma. The patient, a 73-year-old woman, underwent a gastric endoscopy examination, and the histological findings suggested MALT-type gastric lymphoma. Analysis of the immunoglobulin heavy chain (IgH) gene and T cell receptor gamma (TCRgamma) gene revealed monoclonal rearrangement of the TCRgamma gene. The tumor cells exhibited mild atypia and immunoreactivity with anti-CD3, anti-CD8, anti-T-cell intracellular antigen-1, antigranzyme B and antiperforin antibodies, but not with anti-CD20, anti-CD10, and anti-CD79a antibodies. The case was finally diagnosed as gastric T-cell lymphoma with cytotoxic phenotype, and this was confirmed after surgical resection. In cases such as this, small biopsy specimens from the stomach should be examined carefully for low grade B-cell-type malignant lymphoma (MALT lymphoma), because sometimes the proliferating B cells can hide the truly malignant T cells, and rearrangement analysis is useful for diagnosing T-cell malignancy.

PubMed

Establishment of an immortalized cell line from a precancerous lesion of lung adenocarcinoma, and genes highly expressed in the early stages of lung adenocarcinoma development.

Aki Shimada, Junko Kano, Tadashi Ishiyama, Chigusa Okubo, Tatsuo Iijima, Yukio Morishita, Yuko Minami, Yukinori Inadome, Yujian Shu, Shintaro Sugita, Tomoyo Takeuchi, Masayuki Noguchi

Cancer science 96 ( 10 ) 668 - 75 2005.10 [International journal]

Atypical adenomatous hyperplasia (AAH) is classified as a precancerous lesion of lung adenocarcinoma. We established an immortalized AAH cell line (PL16T) and a human non-neoplastic bronchial epithelial cell line (PL16B) from the same patient by transfection with the gene for SV40 large T antigen. The expression profile of PL16T was compared with that of PL16B by the suppression subtractive hybridization method. From 704 selectively hybridized clones, we finally selected 25 fragments of mRNA that showed transcription levels more than three times higher in PL16T than in PL16B. Thirteen (52%) and eight (32%) of them encoded tumor-associated calcium signal transducer 2 (TACSTD2) and S100 calcium binding protein A2 (S100A2), respectively. The high transcription of TACSTD2 and S100A2 in PL16T was confirmed by in situ hybridization. In normal lung tissue, both TACSTD2 and S100A2 were expressed at very low levels, but seven and five of 14 AAH were positive for TACSTD2 and S100A2, respectively. The frequency of TACSTD2 positivity was increased in 16 of 22 bronchioloalveolar carcinomas (BAC) and adenocarcinoma with mixed subtype with BAC component (mixed BAC). Positivity for S100A2 occurred in four of 22 BAC and mixed BAC. The abnormal transcription of TACSTD2 and S100A2 are thought to be unique molecular markers of the preinvasive stage of lung adenocarcinoma.

PubMed

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<SUGITA Shintarou>

Papers - SUGITA Shintarou