Faculty Profiles - IGAWA Takuro

Papers - IGAWA Takuro

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High Prevalence of MYD88 and CD79B Mutations in Primary Sinonasal Diffuse Large B-Cell Lymphoma: Identification of an MCD-like Subtype. Reviewed International journal

Fangli Peng, Takuro Igawa, Tomohiro Urata, Hiroki Kobayashi, Tetsuya Isoda, Sawako Ono, Takehiro Tanaka, Daisuke Ennisshi, Yoshinobu Maeda, Hidetaka Yamamoto

The American journal of surgical pathology 2024.10

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

Primary sinonasal diffuse large B-cell lymphoma (PSDLBCL) is a rare aggressive lymphoma. Recently, genetic classification using Next Generation Sequencing (NGS) demonstrated that PSDLBCL largely consists of the MCD genotype, which has a poor prognosis mainly driven by MYD88 L265P and CD79B gene abnormalities. This study investigated the prevalence and clinicopathological significance of MYD88 L265P and CD79B Y196 mutations using droplet digital PCR in 55 patients with PSDLBCL, as well as the translocation of BCL2/BCL6/c-Myc with FISH. We found mutations in MYD88 L265P (29/55, 52.7%) and CD79B Y196 (20/55, 36.4%). The MCD-like subtype, defined by the mutation of MYD88 and/or CD79B, was found in 32 out of 55 cases (58.2%). This subtype largely consists of non-GCB type (31/32, 96.9%; P<0.01) and double-expressor cases (20/32, 62.5%; P=0.01) compared with the MYD88/CD79B co-wild type, with BCL6 translocation in a small subset (2/32, 6.3%) and no translocations of BCL2 (0/32) or c-Myc (0/32). The MCD-like subtype tended to relapse in specific sites such as the central nervous system, testis, and/or skin compared with the co-wild type (P=0.03), showing poorer outcomes in overall survival (P=0.02) and progression-free survival (P=0.01). In conclusion, our study highlights a high prevalence of MYD88 and CD79B mutations in PSDLBCL, identifying an aggressive MCD-like subtype with a distinct relapse pattern. This molecular subclassification can be helpful for both prognostic prediction and therapeutic strategy in patients with PSDLBCL.

DOI： 10.1097/PAS.0000000000002329

Squamous cell carcinoma initially occurring on the tongue dorsum: a case series report with molecular analysis. Reviewed International journal

Sawako Ono, Katsutoshi Hirose, Shintaro Sukegawa, Kyoichi Obata, Masanori Masui, Kazuaki Hasegawa, Ai Fujimura, Katsumitsu Shimada, Satoko Nakamura, Akari Teramoto, Yumiko Hori, Eiichi Morii, Daisuke Motooka, Takuro Igawa, Takehiro Tanaka, Hitoshi Nagatsuka, Satoru Toyosawa, Hidetaka Yamamoto

Diagnostic pathology 19 ( 1 ) 63 - 63 2024.4

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

BACKGROUND: Squamous cell carcinoma (SCC) of the dorsum of the tongue is extremely rare, and it clinically resembles various benign lesions. Somatic mutations in TP53 and some driver genes were implicated in the development of SCC; however, the somatic genetic characteristics of dorsal tongue SCC remain unknown. With a detailed analysis of gene mutations in dorsal tongue SCC, we aimed to better understand its biology. METHODS: Four cases of SCC initially occurring on the tongue dorsum were evaluated for clinical and histological findings and immunohistochemical expression of p53 and p16. Gene mutations were analyzed using next-generation sequencing with a custom panel of driver genes. RESULTS: We retrospectively investigated 557 cases of tongue SCC, and only four cases of SCC initially occurred on the tongue dorsum. The four patients (cases 1-4) were one woman and three men with a mean age of 53.75 years (range: 15-74 years). Histological analysis revealed well-differentiated SCC. Through molecular analysis, we identified pathogenic somatic mutations, namely, TP53 p.C176F (c.527G > T) in case 3 and TP53 p.R282W (c.844 C > T) in case 4. No pathogenic variants were identified in the PI3K/AKT or RAS/RAF pathways. The p53 immunohistochemical examination revealed a wild-type expression pattern in cases 1-3 and strong expression in case 4. The results of p16 immunostaining were negative in all cases. CONCLUSIONS: We described four previously unreported genetic characteristics of dorsal tongue SCC. Somatic TP53 mutations may contribute to the development of a subset of dorsal tongue SCC; however, more cases with genetic analysis need to be accumulated.

DOI： 10.1186/s13000-024-01487-0

耳下腺に発生したCarcinoma showing thymus-like differentiation(CASTLE)の一例

小野早和子, 西田賢司, 柳井広之, 井川卓朗, 田中健大, 山元英崇

日本病理学会会誌 113 ( 1 ) 346 - 346 2024.2

プロスタグランジンI2製剤投与中の肺動脈性肺高血圧症患者に発症した胃病変に対する病理学的検討

堀川恭佑, 田中健大, 荒島拓馬, 綾田善行, 小野早和子, 井川卓朗, 磯田哲也, 神農陽子, 万波智彦, 山元英崇

日本病理学会会誌 113 ( 1 ) 376 - 376 2024.2

Expression and clinicopathological characteristics of PDX1, PTF1A, and SALL4 in large and small ducts of ectopic pancreas located in gastro-duodenum and jejunum. Reviewed International journal

Mengxi Chen, Takehiro Tanaka, Takuro Igawa, Yanyan Han, Fangli Peng, Zaishun Jin, Tadashi Yoshino

Heliyon 9 ( 7 ) e18241 2023.7

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

An ectopic pancreas is defined as pancreatic tissue outside its normal location, anatomically separated from the pancreas. The transcription factor pancreas/duodenum homeobox protein 1 (PDX1) is involved in maintaining the pancreas and functions in early pancreatic development, beta cell differentiation, and endocrine non beta cells. Pancreatic transcription factor 1 subunit alpha (PTF1A) affects exocrine cell formation and regulation of acinar cell identity, and is expressed in exocrine cells as a transcription factor. The depletion of SALL4 disrupts self-renewal and induces differentiation. To clarify which of PDX1, PTF1A, or SALL4 determines the difference in Heinrich's classification, we examined the localization and number of positive cells. We analyzed the differential expression of PDX1, PTF1A, and SALL4 in large and small ducts in ectopic pancreas by immunohistochemistry. Results showed that the number of PTF1A-positive cells in large ducts was more widespread in type I than in type II in the gastro-duodenum, and more SALL4-positive cells were noticed in large ducts than in small ducts in the gastro-duodenum of type II. Our results revealed that PTF1A might promote exocrine differentiation in developing the pancreatic tissues, and that those with widespread expression differentiate into exocrine cells.

DOI： 10.1016/j.heliyon.2023.e18241

Kimura disease forming a human polyomavirus 6-negative parotid gland nodule with prominent squamous metaplasia in a young female: A case report. Reviewed International journal

Kenji Yorita, Tatsuya Fujii, Toshitaka Nagao, Ichiro Murakami, Yumiko Hashida, Tomonori Higuchi, Masanori Daibata, Makoto Toi, Yoshiyuki Ayada, Takuro Igawa

Radiology case reports 18 ( 5 ) 1933 - 1938 2023.5

Authorship：Last author Language：English

A case of an asymptomatic 19-year-old woman with Kimura disease presenting with a nodule in the right parotid gland is presented. She had a medical history of atopic dermatitis and noticed a mass on her right-side neck. Cervical lymphadenopathy was clinically diagnosed. The initial management plan was to observe the lesion, which had enlarged from 1 cm to 2 cm in diameter 6 months later. An excisional biopsy was performed, and the pathology confirmed an eosinophil-containing inflammatory parotid gland lesion with many squamous nests and cysts, mimicking a parotid gland tumor. High serum immunoglobulin E levels, peripheral blood eosinophilia, and pathological and genetic diagnoses confirmed Kimura disease. The lesion tested negative for human polyomavirus 6. No recurrence was observed 15 months after the biopsy. The prognosis of Kimura disease without human polyomavirus 6 infection may be favorable; however, further validation of this hypothesis is required as only 5 or 6 cases of Kimura disease have been evaluated for this viral infection. Proliferative squamous metaplasia occurring in parotid gland lesions of Kimura disease is rare and may complicate the diagnostic imaging and pathological diagnosis.

DOI： 10.1016/j.radcr.2023.02.027

Immunohistochemistry for IRTA1 and MNDA helps differentiate gastric MALT lymphoma from chronic gastritis/reactive lymphocyte hyperplasia. Reviewed

Yoshiyuki Ayada, Takuro Igawa, Yusuke Naoi, Kyosuke Horikawa, Tetsuya Tabata, Takehiro Tanaka, Tadashi Yoshino

Journal of clinical and experimental hematopathology : JCEH 62 ( 4 ) 195 - 201 2022.12

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

It is difficult to histologically differentiate extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) from chronic gastritis (CG)/ reactive lymphoid hyperplasia (RLH). To determine whether immunohistochemistry for IRTA1 and MNDA can differentiate gastric MALT lymphoma from CG/RLH, we investigated 81 stomach biopsy specimens [Wotherspoon grade (WG) 1, 11 cases; WG 2, 9 cases; WG 3, 20 cases; WG 4, 31 cases; and WG 5, 10 cases]. According to a previously reported algorithm involving PCR for immunoglobulin heavy (IgH) chain locus rearrangement, all 81 cases were divided into three groups: CG/RLH (55 cases), MALT lymphoma (19 cases) groups, and IgH undetectable group (7 cases). We analyzed the CG/RLH and MALT lymphoma groups. The median percentage of IRTA1-positive cells was 0% (range 0%-90.6%) in the CG/RLH group and 43.5% (range 0%-97.6%) in the MALT lymphoma group (p < 0.0001). The median percentage of MNDA-positive cells was 32.4% (range 0%-97.6%) in the CG/RLH group and 55.1% (range 0%-97.6%) in the MALT lymphoma group (p = 0.0044). These results indicate that immunohistochemistry for IRTA1 and MNDA can help differentiate gastric MALT lymphoma from CG/RLH.

DOI： 10.3960/jslrt.22021

Systemic Abscopal Effect of Low-dose Radiotherapy (2 Gy ×2) against Palatine Tonsil Follicular Lymphoma.

Kazuto Togitani, Tadashi Asagiri, Mitsuko Iguchi, Takuro Igawa, Tadashi Yoshino, Kensuke Kojima

Internal medicine (Tokyo, Japan) 61 ( 20 ) 3107 - 3110 2022.10

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

A 52-year-old man presented with palatine tonsillar swelling caused by follicular lymphoma. His tumor burden was low, but exacerbation of snoring and dysphagia was observed. Considering the first wave of coronavirus disease 2019 (COVID-19) pandemic, he received palliative 4-Gy irradiation to the tonsils in 2 fractions, which induced partial regression of tonsillar swellings and eradication of the circulating lymphoma cells. We suggest that low-dose radiotherapy triggered an abscopal effect of lymphoma, which allowed the patient time to receive COVID-19 vaccination before starting immunosuppressive chemo-immunotherapy.

DOI： 10.2169/internalmedicine.8968-21

Luminal administration of biliverdin ameliorates ischemia-reperfusion injury following intestinal transplant in rats. Reviewed International journal

Tsuyoshi Nojima, Takafumi Obara, Hirotsugu Yamamoto, Tetsuya Yumoto, Takuro Igawa, Toshiyuki Aokage, Mizuki Seya, Atsunori Nakao, Hiromichi Naito

Surgery 172 ( 5 ) 1522 - 1528 2022.9

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

BACKGROUND: Intestinal grafts are susceptible to ischemia-reperfusion injury, resulting in the loss of mucosal barrier function and graft failure. Biliverdin is known to exert a variety of cytoprotective functions against oxidative tissue injury. Because the mucosal layer is the primary site of ischemia-reperfusion injury, mucosa-targeting strategies by luminal delivery of reagents might be beneficial. We tested whether intraluminal administration of biliverdin as an adjuvant to standard preservation solutions protected against ischemia-reperfusion injury. METHODS: Orthotopic syngeneic intestinal transplants were performed on Lewis rats after 6 hours of cold preservation. Saline containing biliverdin (10 μM) or without biliverdin was introduced into the lumen of the intestinal grafts immediately before cold preservation. RESULTS: Damage to the intestinal mucosa caused by ischemia-reperfusion injury resulted in severe morphological changes, including blunting of the villi and erosion, and led to significant loss of gut barrier function 3 hours after reperfusion. These changes to the mucosa were notably ameliorated by intraluminal administration of biliverdin. Biliverdin also effectively inhibited upregulation of messenger RNAs for interleukin-6, inducible nitric oxide synthase, and C-C motif chemokine 2. Additionally, biliverdin treatment prevented the loss of expression of claudin-1, a transmembrane, tight-junction barrier protein. The 14-day survival of recipients of biliverdin-treated grafts was significantly improved as compared with the recipients of saline-treated control grafts (83.3% vs 38.9%, P = .030). CONCLUSION: This study demonstrated that luminally delivered biliverdin provides beneficial effects during the transplant of rat small intestinal grafts and could be an attractive therapeutic option in organ transplantation.

DOI： 10.1016/j.surg.2022.07.021

Lung recruitment after cardiac arrest during procurement of atelectatic donor lungs is a protective measure in lung transplantation. Reviewed International journal

Eito Niman, Kentaroh Miyoshi, Toshio Shiotani, Tomohiro Toji, Takuro Igawa, Shinji Otani, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

Journal of thoracic disease 14 ( 8 ) 2802 - 2811 2022.8

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

BACKGROUND: Brain-dead donors are susceptible to pulmonary atelectasis (AT). In procurement surgery, lung recruitment under circulatory conditions and cold-flushing for atelectatic donor lungs often provoke graft injury due to the acute blood inflow. We hypothesized that lung recruitment without blood circulation can mitigate graft injury. This study aimed to examine the benefits of lung recruitment subsequent to cardiac arrest using a porcine lung-transplant model. METHODS: Thirteen donor pigs were categorized into the non-atelectatic (No-AT) group (n=3) representing a healthy control group; AT-BCR group (n=5), in which AT was reverted by conventional blood-circulated recruitment (BCR); and AT-no-BCR group (n=5), in which AT was reverted by no-BCR following circulatory arrest. In the atelectatic donor models, the left main bronchus was ligated for 24 hours prior to lung procurement. Left lung transplantation (LTx) was subsequently performed in the thirteen recipient pigs. After 6 hours evaluation, the recipients were euthanized and the lung grafts were excised. RESULTS: The post-transplant PaO2/FiO2 ratio was significantly higher in the AT-no-BCR group than in the AT-BCR group (P=0.015). Wet/dry ratio, histological findings of graft injury and tissue interleukin-8 expression in the AT-no-BCR group were similar to those of the No-AT group. CONCLUSIONS: Lung recruitment without circulation after circulatory arrest could be more protective for atelectatic donor lung than the conventional procedure.

DOI： 10.21037/jtd-22-226

Luminal Administration of a Water-soluble Carbon Monoxide-releasing Molecule (CORM-3) Mitigates Ischemia/Reperfusion Injury in Rats Following Intestinal Transplantation. Reviewed International journal

Takafumi Obara, Hirotsugu Yamamoto, Toshiyuki Aokage, Takuro Igawa, Tsuyoshi Nojima, Takahiro Hirayama, Mizuki Seya, Michiko Ishikawa-Aoyama, Atsunori Nakao, Roberto Motterlini, Hiromichi Naito

Transplantation 106 ( 7 ) 1365 - 1375 2022.7

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

BACKGROUND: The protective effects of carbon monoxide (CO) against ischemia/reperfusion (IR) injury during organ transplantation have been extensively investigated. Likewise, CO-releasing molecules (CORMs) are known to exert a variety of pharmacological activities via liberation of controlled amounts of CO in organs. Therefore, we hypothesized that intraluminal administration of water-soluble CORM-3 during cold storage of intestinal grafts would provide protective effects against IR injury. METHODS: Orthotopic syngeneic intestinal transplantation was performed in Lewis rats following 6 h of cold preservation in Ringer solution or University of Wisconsin solution. Saline containing CORM-3 (100 µmol/L) or its inactive counterpart (iCORM-3) was intraluminally introduced in the intestinal graft before cold preservation. RESULTS: Histopathological analysis of untreated and iCORM-3-treated grafts revealed a similar erosion and blunting of the intestinal villi. These changes in the mucosa structure were significantly attenuated by intraluminal administration of CORM-3. Intestinal mucosa damage caused by IR injury led to considerable deterioration of gut barrier function 3 h postreperfusion. CORM-3 significantly inhibited upregulation of proinflammatory mRNA levels, ameliorated intestinal morphological changes, and improved graft blood flow and mucosal barrier function. Additionally, CORM-3-treated grafts increased recipient survival rates. Pharmacological blockade of soluble guanylyl cyclase activity significantly reversed the protective effects conferred by CORM-3, indicating that CO partially mediates its therapeutic actions via soluble guanylyl cyclase activation. CONCLUSIONS: Our study demonstrates that luminally delivered CORM-3 provides beneficial effects in cold-stored rat small intestinal grafts and could be an attractive therapeutic application of CO in the clinical setting of organ preservation and transplantation.

DOI： 10.1097/TP.0000000000004007

Luminal Administration of a Water-soluble Carbon Monoxide-releasing Molecule (CORM-3) Mitigates Ischemia/Reperfusion Injury in Rats Following Intestinal Transplantation. Reviewed International journal

Takafumi Obara, Hirotsugu Yamamoto, Toshiyuki Aokage, Takuro Igawa, Tsuyoshi Nojima, Takahiro Hirayama, Mizuki Seya, Michiko Ishikawa-Aoyama, Atsunori Nakao, Roberto Motterlini, Hiromichi Naito

Transplantation 106 ( 7 ) 1365 - 1375 2021.12

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

BACKGROUND: The protective effects of carbon monoxide (CO) against ischemia/reperfusion (IR) injury during organ transplantation have been extensively investigated. Likewise, CO-releasing molecules (CORMs) are known to exert a variety of pharmacological activities via liberation of controlled amounts of CO in organs. Therefore, we hypothesized that intraluminal administration of water-soluble CORM-3 during cold storage of intestinal grafts would provide protective effects against IR injury. METHODS: Orthotopic syngeneic intestinal transplantation was performed in Lewis rats following 6 h of cold preservation in Ringer solution or University of Wisconsin solution. Saline containing CORM-3 (100 µmol/L) or its inactive counterpart (iCORM-3) was intraluminally introduced in the intestinal graft before cold preservation. RESULTS: Histopathological analysis of untreated and iCORM-3-treated grafts revealed a similar erosion and blunting of the intestinal villi. These changes in the mucosa structure were significantly attenuated by intraluminal administration of CORM-3. Intestinal mucosa damage caused by IR injury led to considerable deterioration of gut barrier function 3 h postreperfusion. CORM-3 significantly inhibited upregulation of proinflammatory mRNA levels, ameliorated intestinal morphological changes, and improved graft blood flow and mucosal barrier function. Additionally, CORM-3-treated grafts increased recipient survival rates. Pharmacological blockade of soluble guanylyl cyclase activity significantly reversed the protective effects conferred by CORM-3, indicating that CO partially mediates its therapeutic actions via soluble guanylyl cyclase activation. CONCLUSION: Our study demonstrates that luminally delivered CORM-3 provides beneficial effects in cold-stored rat small intestinal grafts and could be an attractive therapeutic application of CO in the clinical setting of organ preservation and transplantation.

DOI： 10.1097/TP.0000000000004007

Invasion of small cell lung cancer into the limbic system from leptomeningeal metastases. Reviewed International journal

Hisao Higo, Takuro Igawa, Katsuhiro Matsuoka, Hiromichi Kawaji, Noriyuki Suzaki, Takuya Nagata, Masako Nagayama, Masaomi Marukawa

Respiratory medicine case reports 33 101417 - 101417 2021

Language：English

The diagnosis of leptomeningeal metastases is sometimes difficult when the cytology of cerebrospinal fluid is negative. We report a rare case of leptomeningeal metastases that required differentiation from paraneoplastic limbic encephalitis. A 67-year-old man with extensive-stage small cell lung cancer was admitted for a sudden decrease in the level of consciousness. He suffered memory disturbances that began the day before admission. Diffusion-weighted and fluid-attenuated inversion recovery images of brain magnetic resonance imaging (MRI) showed bilateral symmetric areas of hyperintensity in the hippocampus, amygdala, insular cortex, and medial temporal lobe; contrast enhancement was positive. Cytology of the cerebrospinal fluid (CSF) was negative. Anti-N-methyl-d-aspartate receptor antibody and herpes simplex virus DNA were not detected in the CSF. Paraneoplastic Limbic encephalitis was suspected due to his symptoms and brain MRI scan. The patient developed generalized seizures after admission. High-dose methylprednisolone and intravenous immune globulin were administered, but his condition did not improve. Uncontrollable seizures persisted and he died in the hospital at day 13. Autopsy revealed leptomeningeal metastasis and invasion of cancer cells into the limbic system. Contrast-enhanced MRI should be performed even if limbic encephalitis is suspected, and leptomeningeal metastases should be suspected if the lesions are enhanced.

DOI： 10.1016/j.rmcr.2021.101417

Pulmonary Manifestations of Plasma Cell Type Idiopathic Multicentric Castleman Disease: A Clinicopathological Study in Comparison with IgG4-Related Disease. Reviewed International journal

Midori Filiz Nishimura, Takuro Igawa, Yuka Gion, Sakura Tomita, Dai Inoue, Akira Izumozaki, Yoshifumi Ubara, Yoshito Nishimura, Tadashi Yoshino, Yasuharu Sato

Journal of personalized medicine 10 ( 4 ) 2020.12

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

Plasma cell type idiopathic multicentric Castleman disease (PC-iMCD) occasionally manifests as parenchymal lung disease. This study aimed to elucidate the detailed clinicopathological features of lung lesions in PC-iMCD and compare the findings with those in immunoglobulin (Ig) G4-related disease (IgG4-RD), the most difficult differential diagnosis of PC-iMCD. We analyzed the clinicopathological findings and immunohistochemical expression patterns of interleukin-6 (IL-6) and Igs in lung specimens from 16 patients with PC-iMCD and 7 patients with IgG4-RD. Histologically, pulmonary PC-iMCD could not be differentiated from IgG4-RD based on lesion distribution patterns, the number of lymphoid follicles and obliterative vasculitis, or fibrosis types. The eosinophil count was higher in the IgG4-RD group than in the PC-iMCD group (p = 0.004). The IgG4/IgG-positive cell ratio was significantly higher in the IgG4-RD group (p < 0.001). The IgA-positive cell count and IL-6 expression intensity were higher in the PC-iMCD group than in the IgG4-RD group (p < 0.001). Based on these findings, we proposed a new diagnostic approach to differentiate lung lesions of PC-iMCD and IgG4-RD. Our approach can be utilized to stratify patients with suspected lung-dominant PC-iMCD to identify candidates for strong immunosuppressive treatment, including IL-6 blockade, at an early stage.

DOI： 10.3390/jpm10040269

Deletion of BART miRNA-encoding cluster in Epstein-Barr virus DNA in classic Hodgkin lymphoma. Reviewed International journal

Akihiro Kawatsuki, Takuro Igawa, Tomohiro Urata, Takehiro Tanaka, Yasuharu Sato, Tadashi Yoshino

Pathology international 70 ( 12 ) 1032 - 1033 2020.12

Adult T-cell Leukemia-lymphoma with Primary Breast Involvement: A Case Report and Literature Review.

Hiroki Kobayashi, Noboru Asada, Takuro Igawa, Masaya Abe, Yusuke Meguri, Daisuke Ennishi, Hisakazu Nishimori, Nobuharu Fujii, Ken-Ichi Matsuoka, Tadashi Yoshino, Yoshinobu Maeda

Internal medicine (Tokyo, Japan) 59 ( 21 ) 2757 - 2761 2020.11

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

Breast involvement of Adult T-cell leukemia-lymphoma (ATLL) is extremely rare, and the data on the characteristics are limited. We herein describe a 49-year-old woman who presented with skin involvement of ATLL. Positron emission tomography/computed tomography showed bilateral breast lesions. Although the patient once achieved a complete metabolic response, a relapse of her ATLL occurred. The patient received subsequent allogeneic hematopoietic stem cell transplantation (HSCT). To our knowledge, only four cases of ATLL with breast involvement have previously been reported, and the prognoses have generally been poor. Breast lesions of ATLL have aggressive features, and intensive systemic chemotherapy and HSCT are required to improve survival.

DOI： 10.2169/internalmedicine.5077-20

Luminal preloading with hydrogen-rich saline ameliorates ischemia-reperfusion injury following intestinal transplantation in rats. Reviewed International journal

Hirotsugu Yamamoto, Toshiyuki Aokage, Takuro Igawa, Takahiro Hirayama, Mizuki Seya, Michiko Ishikawa-Aoyama, Tsuyoshi Nojima, Atsunori Nakao, Hiromichi Naito

Pediatric transplantation 24 ( 7 ) e13848 2020.11

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

Prolonged intestinal cold storage causes considerable mucosal breakdown, which could bolster bacterial translocation and cause life-threatening infection for the transplant recipient. The intestine has an intraluminal compartment, which could be a target for intervention, but has not yet been fully investigated. Hydrogen gas exerts organ protection and has used been recently in several clinical and basic research studies on topics including intestinal transplantation. In this study, we aimed to investigate the cytoprotective efficacy of intraluminally administered hydrogen-rich saline on cold IR injury in intestinal transplantation. Isogeneic intestinal transplantation with 6 hours of cold ischemia was performed on Lewis rats. Hydrogen-rich saline (H2 concentration at 5 ppm) or normal saline was intraluminally introduced immediately before preservation. Graft intestine was excised 3 hours after reperfusion and analyzed. Histopathological analysis of control grafts revealed blunting of the villi and erosion. These mucosal changes were notably attenuated by intraluminal hydrogen. Intestinal mucosa damage caused by IR injury led to considerable deterioration of gut barrier function 3 h post-reperfusion. However, this decline in permeability was critically prevented by hydrogen treatment. IR-induced upregulation of proinflammatory cytokine mRNAs such as IL-6 was mitigated by hydrogen treatment. Western blot revealed that hydrogen treatment regulated loss of the transmembrane protein ZO-1. Hydrogen-rich saline intraluminally administered in the graft intestine modulated IR injury to transplanted intestine in rats. Successful abrogation of intestinal IR injury with a novel strategy using intraluminal hydrogen may be easily clinically applicable and will compellingly improve patient care after transplantation.

DOI： 10.1111/petr.13848

Clinicopathological significance of CD79a expression in classic Hodgkin lymphoma. Reviewed

Akio Sakatani, Takuro Igawa, Takeshi Okatani, Megumu Fujihara, Hideki Asaoku, Yasuharu Sato, Tadashi Yoshino

Journal of clinical and experimental hematopathology : JCEH 60 ( 3 ) 78 - 86 2020.9

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

Classic Hodgkin lymphoma (CHL) is a lymphoid neoplasia characterized by the presence of large tumor cells, referred to as Hodgkin and Reed-Sternberg (HRS) cells, originating from B-cells in an inflammatory background. As the clinical significance of B-cell markers has yet to be fully elucidated, this study aimed to clarify the clinicopathological significance of CD79a in 55 patients with CHL. They were immunohistochemically divided into two groups, comprising of 20 CD79a-positive and 35 CD79a-negative patients. There was no significant correlation between CD79a and CD20 expression (rs = 0.125, P = 0.362). CD79a-positive patients were significantly older at onset (P = 0.011). There was no significant correlation between CD79a-positivity and clinical stage (P = 0.203), mediastinal involvement (P = 0.399), extranodal involvement (P = 0.749), or laboratory findings, including serum levels of lactate dehydrogenase (P = 1) and soluble interleukin-2 receptor (P = 0.251). There were significant differences in overall survival (OS) (P = 0.005) and progression-free survival (PFS) (P = 0.007) between CD79a-positive and CD79a-negative patients (5-year OS: 64.6% and 90.5%; 5-year PFS: 44.0% and 76.6%, respectively). Five patients in whom the majority (> 80%) of HRS cells expressed CD79a consisted of 4 males and 1 female aged between 52 and 81 years; 4 of them were in a limited clinical stage. We concluded that CD79a-positive CHL may have unique clinicopathological features.

DOI： 10.3960/jslrt.20010

Hemosiderin deposition in lymph nodes of patients with plasma cell-type Castleman disease. Reviewed

Yanyan Han, Takuro Igawa, Kyohei Ogino, Asami Nishikori, Yuka Gion, Tadashi Yoshino, Yasuharu Sato

Journal of clinical and experimental hematopathology : JCEH 60 ( 1 ) 1 - 6 2020.3

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

Plasma cell-type Castleman disease (PCD) is a rare idiopathic atypical lymphoproliferative disorder. It is difficult to differentiate between PCD and IgG4-related disease (IgG4-RD) based on histology alone. As PCD often presents with abundant hemosiderin deposition, lymph node lesions obtained from 22 PCD patients and 12 IgG4-RD patients were analyzed using Prussian blue staining to clarify whether hemosiderin deposition is effective in distinguishing between these two diseases. The analysis disclosed that hemosiderin was more densely deposited in PCD than in IgG4-RD. The median number of Prussian blue-positive cells ± standard deviation (SD) in PCD and IgG4-RD cases was 13 ± 36 cells/3HPFs and 4 ± 8 cells/3HPFs (P = 0.034), respectively. In addition, we analyzed the relationship between hemosiderin deposition and levels of serum interleukin (IL)-6, serum C-reactive protein (CRP), and anemia-related biomarkers. We found that hemosiderin deposition was significantly correlated with the level of serum CRP (P = 0.045); however, no significant correlation was observed between hemosiderin deposition and serum IL-6 levels (P = 0.204). A non-significant positive correlation was observed between hemosiderin deposition and serum hemoglobin levels (P=0.09). Furthermore, no significant correlation was observed between hemosiderin deposition and serum iron levels (P = 0.799). In conclusion, hemosiderin deposition characteristically observed in PCD may be related to the inflammatory aggressiveness of the disease and could be used for its differential diagnosis.

DOI： 10.3960/jslrt.19037

Triple-negative pleomorphic lobular carcinoma and expression of androgen receptor: Personal case series and review of the literature. Reviewed International journal

Kohei Taniguchi, Shinichi Takada, Masako Omori, Takuro Igawa, Midori Filiz Nishimura, Toshiaki Morito, Kouichi Ichimura, Tadashi Yoshino

PloS one 15 ( 7 ) e0235790 2020

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

Pleomorphic lobular carcinoma (PLC) is a histological variant of invasive lobular carcinoma (ILC) and is associated with worse prognosis than classical ILC. It exhibits a greater degree of cellular atypia and pleomorphism and is occasionally accompanied with apocrine morphology. We investigated the immunohistochemical characteristics of samples from 31 Japanese patients with PLC to elucidate the clinicopathological characteristics of PLC including androgen receptor (AR) immunoreactivity. The surrogate molecular subtypes were luminal A-like, luminal B-like, luminal B-like/HER2, HER2-type, and triple-negative in 5, 4, 3, 5, and 14 cases, respectively. AR was positive in 92.8% (13/14) of the triple-negative PLC cases and 100% (10/10) of the non-triple-negative PLC cases. Disease-specific survival was worse in patients with histological grade 3 PLCs than in those with histological grade 2 PLCs (p = 0.007). However, there was no significant difference in the progression-free survival between the two groups (p = 0.152). No other clinicopathological characteristics were associated with prognosis. These results reveal that PLC exhibits various surrogate molecular subtypes and that the triple-negative subtype frequently expresses AR. The observed molecular apocrine differentiation implicates that triple-negative PLC can be categorized into the luminal AR subtype. Furthermore, AR-targeted therapy might be useful for patients with triple-negative PLC.

DOI： 10.1371/journal.pone.0235790

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