Faculty Profiles - SATO Yasuharu

Papers - SATO Yasuharu

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Atypical lymphoplasmacytic and immunoblastic proliferation: A Systematic Review Reviewed

Nishimura Midori Filiz, Takahashi Toshiaki, Takaoka Kensuke, Macapagal Sharina, Wannaphut Chalothorn, Nishikori Asami, Toda Hiroko, Nishimura Yoshito, Sato Yasuharu

Journal of Clinical and Experimental Hematopathology 64 ( 2 ) 97 - 106 2024

Authorship：Last author Language：English Publisher：The Japanese Society for Lymphoreticular Tissue Research

Atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) was first reported in 1984 as characteristic histological findings in lymph nodes associated with autoimmune diseases, but it has not been clearly defined to date. To summarize the histological characteristics and clinical diagnoses associated with ALPIBP, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including “atypical lymphoplasmacytic and immunoblastic lymphadenopathy” from their inception to December 27, 2023. We also summarized the courses of three cases with a pathological diagnosis of ALPIBP. Nine articles with 52 cases were included. Among the total of 55 cases, including the three from our institution, the median age of the cases was 63.5 years with a female predominance (69.5%). Lymphadenopathy was generalized in 65.6% and regional in 34.4% of cases. RA (24.4%), SLE (24.4%), and autoimmune hemolytic anemia (20.0%), were common clinical diagnoses. A combination of cytotoxic chemotherapy was used in 15.6% of cases due to the suspicion of malignancy. Nodal T-follicular helper cell lymphoma, angioimmunoblastic type, methotrexate-associated lymphoproliferative disorders, and IgG4-related diseases were listed as important diseases that need to be pathologically differentiated from ALPIBP. This review summarizes the current understanding of the characteristics of ALPIBP. Given that underrecognition of ALPIBP could lead to overdiagnosis of hematological malignancy and unnecessary treatment, increased awareness of the condition in pathologists and clinicians is crucial.

DOI： 10.3960/jslrt.24007

T-cell receptor gamma gene rearrangement analysis of classic Hodgkin lymphoma using a BIOMED-2 assay: a paraffin-embedded tissue analysis of one hundred cases. Reviewed

Katsuyoshi Takata, Tomoko Miyata-Takata, Asami Nishikori, Tomoka Haratake, Yasuharu Sato

Journal of clinical and experimental hematopathology : JCEH 64 ( 2 ) 138 - 143 2024

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

In the new WHO classifications of haematolymphoid tumours (WHO-HAEM5), classic Hodgkin lymphoma (cHL) is categorized into B-cell lymphoid proliferations and lymphomas. Although the majority of Hodgkin Reed-Sternberg (HRS) cells are of germinal center B-cell origin with some defects of B-cell transcription factors, they rarely express T-cell antigens or cytotoxic molecules. Clonality analyses on cHL samples using BIOMED-2 have been reported by several groups; however, those studies were only focused on Ig regions, including IgH, Ig-kappa, and Ig-lambda, and TCR-γ clonality analysis of cHL has not yet been explored. Here, we investigated TCR-γ gene rearrangement for one hundred cases using a PCR-based method. Four of one hundred (4%) cases showed TCR-γ clonal peaks. Of these, three were at an advanced stage and one patient died of the disease. To clarify whether HRS cells showed T-cell clonality or not, we performed PCR analysis using DNAs of microdissected HRS cells. Three samples showed identical clonal peaks with bulk specimens. Our results indicate that cHL is a heterogeneous disease of mainly B-cell and rarely T-cell origin with a special phenotype. Further molecular studies are warranted.

DOI： 10.3960/jslrt.24027

Frequent CDKN2B/P15 and DAPK1 methylation in duodenal follicular lymphoma is related to duodenal reactive lymphoid hyperplasia. Reviewed

Katsuyoshi Takata, Tomoko Miyata-Takata, Yasuharu Sato

Journal of clinical and experimental hematopathology : JCEH 64 ( 2 ) 129 - 137 2024

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

Duodenal type follicular lymphoma (DFL), a rare entity of follicular lymphoma (FL), is clinically indolent and is characterized by a low histological grade compared with nodal follicular lymphoma (NFL). Our previous reports revealed that DFL shares characteristics of both NFL and mucosa-associated lymphoid tissue (MALT) lymphoma in terms of clinical and biological aspects, suggesting its pathogenesis may involve antigenic stimulation. In contrast to NFL, the genomic methylation status of DFL is still challenging. Here, we determined the methylation profiles of DNAs from patients with DFL (n = 12), NFL (n = 10), duodenal reactive lymphoid hyperplasia (D-RLH) (n = 7), nodal reactive lymphoid hyperplasia (N-RLH) (n = 5), and duodenal samples from normal subjects (NDU) (n = 5) using methylation specific PCR of targets previously identified in MALT lymphoma (CDKN2B/P15, CDKN2A/P16, CDKN2C/P18, MGMT, hMLH-1, TP73, DAPK, HCAD). DAPK1 was frequently methylated in DFL (9/12; 75%), NFL (9/10; 90%), and D-RLH (5/7; 71%). CDKN2B/P15 sequences were methylated in six DFL samples and in only one NFL sample. Immunohistochemical analysis showed that p15 expression inversely correlated with methylation status. Genes encoding other cyclin-dependent kinase inhibitors (CDKN2A/P16, CDKN2C/P18) were not methylated in DFL samples. Methylation of the genes of interest was not detected in DNAs from D-RLH, except for DAPK1, and the difference in the extent of methylation between NDU and D-RLH was statistically significant (P = 0.013). Our results suggest that D-RLH serves as a reservoir for the development of DFL and that methylation of CDKN2B/P15 plays an important role in this process.

DOI： 10.3960/jslrt.24020

Primary Thyroid Lymphoma: Clinical Factors Predicting the Possibility of Diffuse Large B-Cell Lymphoma. Reviewed International journal

Akifumi Kariya, Tomoyasu Tachibana, Yasushi Hiramatsu, Yoji Wani, Jun-Ya Matsumoto, Chieko Furukawa, Asuka Sato, Yuto Naoi, Yorihisa Orita, Yasuharu Sato, Mizuo Ando

Ear, nose, & throat journal 1455613231218130 - 1455613231218130 2023.12

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

Aims: Among primary thyroid lymphomas (PTLs), diffuse large B-cell lymphoma (DLBCL) has a poorer prognosis than other indolent lymphomas such as mucosa-associated lymphoid tissue (MALT) or follicular lymphoma (FL). However, the clinical differences between DLBCL and indolent lymphoma remain unclear. Therefore, this retrospective study on PTL was aimed at investigating the clinical differences between DLBCL and indolent lymphomas and identifying the factors differentiating DLBCL from indolent lymphomas. Materials and Methods: Medical records of 28 patients diagnosed with PTL and treated at our institution between 2005 and 2022 were retrospectively analyzed. Data on the following clinical variables were extracted: sex, age, symptoms (pain and dysphagia), ultrasonographic appearance patterns, the presence of airway stenosis on computed tomography and laryngeal endoscopy, blood test results, disease stage, and pathological diagnosis. Results: In all, 13 patients were histologically diagnosed with DLBCL, 12 with MALT lymphoma, and 3 with FL. Significant differences in disease-specific survival rates were evident between the DLBCL and indolent lymphoma groups (68.2 vs 100%, P = .043). High lactate dehydrogenase levels (>230 U/mL) and airway stenosis were observed only in patients with DLBCL. Multivariate analysis identified that the presence of a linear echoic strand pattern and the absence of an echoic nodular pattern on ultrasound were independently associated with DLBCL (P = .0497 and .012, respectively). Conclusion: DLBCL can cause airway stenosis. The linear echogenic strand pattern and the absence of a nodular pattern should be recognized as predictive factors of DLBCL.

DOI： 10.1177/01455613231218130

Pediatric IgG4-related disease: a descriptive review. Reviewed International journal

Satoshi Hara, Misaki Yoshida, Hajime Sanada, Yasunori Suzuki, Yasuharu Sato, Ichiro Mizushima, Mitsuhiro Kawano

Expert review of clinical immunology 1 - 23 2023.10

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

INTRODUCTION: IgG4-related disease (IgG4-RD) is an immune-mediated systemic fibroinflammatory condition characterized by serum IgG4 elevation and IgG4-positive plasma cell infiltration into various organs. It generally occurs in elderly males. Pediatric cases have been reported, albeit rarely, accordingly lack of recognition of such cases could delay therapeutic intervention leading to poorer outcomes. AREAS COVERED: The present review is a descriptive review of all published case reports, cohort studies, and reviews of pediatric IgG4-RD listed in PubMed. Characteristics of pediatric IgG4-RD were clarified, including sex, organ involvement, serological and histological findings, and treatment. We assessed how many published cases met current classification and comprehensive diagnostic criteria. EXPERT OPINION: The characteristics of pediatricIgG4-RD differed from adult IgG4-RD in terms of sex and involved organs. There was no clear male dominance in numbers of cases, and surface organ involvement such as ophthalmic diseases were more common in the pediatric IgG4-RD. Organ involvement tended to be indolent and unilateral, causing difficulty in definitively diagnosing pediatric IgG4-RD. Only about 20% of published cases met IgG4-RD classification or comprehensive diagnostic criteria. Physicians should be careful in diagnosing pediatric IgG4-RD after excluding mimickers. International collaboration toward high-quality evidence to support diagnosis and treatment of pediatric IgG4-RD is advised.

DOI： 10.1080/1744666X.2023.2274358

Near-infrared photoimmunotherapy for salivary duct carcinoma. Reviewed International journal

Takuma Makino, Yasuharu Sato, Kensuke Uraguchi, Yuto Naoi, Yujiro Fukuda, Mizuo Ando

Auris, nasus, larynx 2023.9

Language：English

In Japan, near-infrared photoimmunotherapy (NIR-PIT) was introduced in 2021 as a treatment option for unresectable recurrent head and neck cancer. The treatment targets the epidermal growth factor receptor (EGFR), which is overexpressed in 80-90 % of head and neck squamous cell carcinoma (HNSCC). NIR-PIT should theoretically show therapeutic efficacy if EGFR is expressed, even in nonsquamous cell carcinomas (non-SCC). To the best of our knowledge, there are no case reports of NIR-PIT for non-SCC. We performed NIR-PIT in a patient with non-SCC of the head and neck region. After performing two NIR-PIT treatments, small free clusters of residual tumor cells were observed. Immunostaining in this specimen revealed EGFR expression in residual tumor cells. The residual tumor cells had been irradiated sufficiently to achieve necrosis. It is suggested that not only laser irradiation and expression of EGFR but also other factors are involved in the efficacy of this treatment. Further investigation for these other factors is warranted.

DOI： 10.1016/j.anl.2023.09.006

Distribution and clinical impact of molecular subtypes with Dark Zone signature of DLBCL in a Japanese real-world study. Reviewed International journal

Tomohiro Urata, Yusuke Naoi, Aixiang Jiang, Merrill Boyle, Kazutaka Sunami, Toshi Imai, Yuichiro Nawa, Yasushi Hiramatsu, Kazuhiko Yamamoto, Soichiro Fujii, Isao Yoshida, Tomofumi Yano, Ryota Chijimatsu, Hiroyuki Murakami, Kazuhiro Ikeuchi, Hiroki Kobayashi, Katsuma Tani, Hideki Ujiie, Hirofumi Inoue, Shuta Tomida, Akira Yamamoto, Takumi Kondo, Hideaki Fujiwara, Noboru Asada, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Keisuke Sawada, Shuji Momose, Jun-Ichi Tamaru, Asami Nishikori, Yasuharu Sato, Tadashi Yoshino, Yoshinobu Maeda, David W Scott, Daisuke Ennishi

Blood advances 2023.8

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

The distribution and clinical impact of cell-of-origin (COO) subtypes of diffuse large B-cell lymphoma (DLBCL) outside Western countries remain unknown. Recent literature also suggests that there is an additional COO subtype associated with the germinal center dark zone, that warrants wider validation to generalize clinical relevance. Here, we assembled a cohort of Japanese patients with untreated DLBCL and determined the refined COO subtypes, that include the dark zone signature (DZsig), using the NanoString DLBCL90 assay. To compare the distribution and clinical characteristics of the molecular subtypes, we used a dataset from the cohort of BC Cancer (BCC) (n = 804). Of the 1050 patients where DLBCL90 assay was successfully performed in our cohort, 35%, 45%, and 6% of patients were identified to be germinal center B-cell-like (GCB)-DLBCL, activated B-cell-like (ABC)-DLBCL, and DZsigpos-DLBCL, respectively, with the highest prevalence of ABC-DLBCL differing significantly from that of BCC (P < 0.001). GCB-DLBCL, ABC-DLBCL, and DZsigpos-DLBCL were associated with two-year overall survival rates of 88%, 75%, and 66%, respectively (P < 0.0001), with patients of the DZsigpos-DLBCL having the poorest prognosis. In contrast, GCB-DLBCL without DZsig showed excellent outcomes following rituximab-containing immunochemotherapy. DZsigpos-DLBCL was associated with the significant enrichment of tumors with CD10 expression, concurrent MYC/BCL2 expression, and depletion of microenvironmental components (all P < 0.05). These results provide evidence of the distinct distribution of clinically relevant molecular subtypes in Japanese DLBCL and that refined COO, as measured by the DLBCL90 assay, is a robust prognostic biomarker that is consistent across geographical areas.

DOI： 10.1182/bloodadvances.2023010402

Comparison of serum sIL-2R and LDH levels in patients with intravascular large B-cell lymphoma and patients with advanced stage diffuse large B-cell lymphoma Reviewed

Yuki Hirami, Midori Filiz Nishimura, Tomohiro Urata, Michiko Morimoto, Yukina Maekawa, Tadashi Yoshino, Yoshito Nishimura, Yasuharu Sato

Journal of Clinical and Experimental Hematopathology 63 ( 1 ) 25 - 31 2023.1

A Case of Adolescent-onset TAFRO Syndrome with Malignant Nephrosclerosis-like Lesions. Reviewed

Yuki Nakayama, Hiroki Mizuno, Naoki Sawa, Tatsuya Suwabe, Masayuki Yamanouchi, Daisuke Ikuma, Eiko Hasegawa, Junichi Hoshino, Akinari Sekine, Yuki Oba, Kei Kono, Keiichi Kinowaki, Kenichi Ohashi, Kodai Suzuki, Yasuharu Sato, Akira Shimizu, Yutaka Yamaguchi, Yoshifumi Ubara

Internal medicine (Tokyo, Japan) 62 ( 15 ) 2223 - 2229 2022.12

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

A 16-year-old Japanese girl developed a fever, thrombocytopenia, and renal dysfunction. Treatment was started with steroids, but cervical lymphadenopathy and ascites developed. A lymph node biopsy indicated TAFRO syndrome. The patient's renal function deteriorated, and dialysis was started. Refractory hypertension and subsequent encephalopathy developed. Treatment was started with an anti-IL-6 receptor antibody and an anti-CD20 monoclonal antibody. A kidney biopsy showed malignant nephrosclerosis-like microangiopathy and glomerular collapse due to narrowing of the small arteries. The majority of TAFRO syndrome cases are adult-onset, with glomerular microangiopathy. To our knowledge, this is the first report of adolescent-onset TAFRO syndrome presenting with malignant nephrosclerosis-like lesions associated with hypertension.

DOI： 10.2169/internalmedicine.0529-22

Utility of renal biopsy in differentiating idiopathic multicentric Castleman disease from IgG4-related disease. Reviewed

Miharu Kawanishi, Fumika Kamei, Hirotaka Sonoda, Masafumi Oba, Shohei Fukunaga, Masahiro Egawa, Takashi Koyama, Yasuharu Sato, Kazuaki Tanabe, Takafumi Ito

CEN case reports 12 ( 2 ) 242 - 248 2022.11

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

Idiopathic multicentric Castleman disease (iMCD) is a subtype of human herpesvirus type 8 (HHV-8)-related Castleman disease that causes multi-organ damage, including kidney damage due to polyclonal lymphoproliferation and interleukin (IL)-6-induced cytokine storm. However, its renal pathological findings are unclear. We report the case of a woman in her 80 s who was diagnosed with iMCD based on renal pathological findings. Five years ago, hypergammaglobulinemia was detected, and her renal function declined. Renal biopsy revealed plasma cells infiltrating the stroma. Immunostaining revealed numerous IgG4-positive plasma cells. The serum IgG4 level was high, and she was initially diagnosed with IgG4-related disease (IgG4-RD) and treated with steroids. However, the therapeutic effect was poor. On re-examination, computed tomography revealed lymphadenopathy around the aorta and spleen. Renal histopathology showed numerous IL-6-positive plasma cells. Anemia and C-reactive protein (CRP) positivity persisted despite steroid administration. HHV-8 was negative, and polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome was not suspected. Thus, iMCD was diagnosed. Based on previous reports, there is no significant difference in IgG4 levels between iMCD and IgG4-RD, and IgG4-positive plasma cell infiltrates were observed in iMCD-affected organs. Therefore, it may be difficult to distinguish iMCD from IgG4-RD. In this case, high-serum IL-6 and CRP were observed, which are usually not seen in IgG4-RD but are common findings in iMCD, leading to the diagnosis. Patients with deep lymphadenopathy may be diagnosed with iMCD based on renal pathological findings. Renal biopsy is recommended for patients with suspected iMCD and decreased renal function.

DOI： 10.1007/s13730-022-00751-w

Clinical characteristics and outcomes of Castleman disease: a multicenter Consortium study of 428 patients with 15-year follow-up. Reviewed International journal

Wanying Liu, Qingqing Cai, Tiantian Yu, Paolo Strati, Frederick B Hagemeister, Qiongli Zhai, Mingzhi Zhang, Ling Li, Xiaosheng Fang, Jianyong Li, Ruifang Sun, Shanxiang Zhang, Hanjin Yang, Zhaoming Wang, Wenbian Qian, Noriko Iwaki, Yasuharu Sato, Eric Oksenhendler, Zijun Y Xu-Monette, Ken H Young, Li Yu

American Journal of Cancer Research 12 ( 9 ) 4227 - 4240 2022.10

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

Castleman disease (CD) has been reported as a group of poorly understood lymphoproliferative disorders, including unicentric CD (UCD) and idiopathic multicentric CD (iMCD) which are human immunodeficiency virus (HIV) negative and human herpes virus 8 (HHV-8) negative. The clinical and independent prognostic factors of CD remain poorly elucidated. We retrospectively collected the clinical information of 428 patients with HIV and HHV-8 negative CD from 12 large medical centers with 15-year follow-up. We analyzed the clinicopathologic features of 428 patients (248 with UCD and 180 with iMCD) with a median age of 41 years. The histology subtypes were hyaline-vascular (HV) histopathology for 215 patients (56.58%) and plasmacytic (PC) histopathology for 165 patients (43.42%). Most patients with UCD underwent surgical excision, whereas the treatment strategies of patients with iMCD were heterogeneous. The outcome for patients with UCD was better than that for patients with iMCD, 5-year overall survival (OS) rates were 95% and 74%, respectively. In further analysis, a multivariate analysis using a Cox regression model revealed that PC subtype, hepatomegaly and/or splenomegaly, hemoglobin ≤ 80 g/L, and albumin ≤ 30 g/L were independent prognostic factors of CD for OS. The model of iMCD revealed that age > 60 years, hepatomegaly and/or splenomegaly, and hemoglobin ≤ 80 g/L were independent risk factors. In UCD, single-factor analysis identified two significant risk factors: hemoglobin ≤ 100 g/L and albumin ≤ 30 g/L. Our study emphasizes the distinction of clinical characteristics between UCD and iMCD. The importance of poor risk factors of different clinical classifications may direct more precise and appropriate treatment strategies.

Neuropeptide Y Antagonizes Development of Pulmonary Fibrosis Through IL-1β Inhibition. Reviewed International journal

Junko Itano, Akihiko Taniguchi, Satoru Senoo, Noboru Asada, Yuka Gion, Yuria Egusa, Lili Guo, Naohiro Oda, Kota Araki, Yasuharu Sato, Shinichi Toyooka, Katsuyuki Kiura, Yoshinobu Maeda, Nobuaki Miyahara

American journal of respiratory cell and molecular biology 67 ( 6 ) 654 - 665 2022.9

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

Neuropeptide Y, a 36-amino acid residue polypeptide, distributed throughout the nervous system, acts on various immune cells in many organs, including the respiratory system. However, little is known about its role in the pathogenesis of pulmonary fibrosis. This study was performed to determine the effects of neuropeptide Y on pulmonary fibrosis. Neuropeptide Y-deficient and wild-type mice were intratracheally administered bleomycin. Inflammatory cells, cytokine levels, and morphological morphometry of the lungs were analyzed. Serum neuropeptide Y levels were also measured in idiopathic pulmonary fibrosis patients and healthy controls. Neuropeptide Y-deficient mice exhibited significantly enhanced pulmonary fibrosis and higher IL-1β levels in the lungs compared to wild-type mice. Exogenous neuropeptide Y treatment suppressed the development of bleomycin-induced lung fibrosis and decreased IL-1β levels in the lungs. Moreover, IL-1β neutralization in neuropeptide Y-deficient mice attenuated the fibrotic changes. Neuropeptide Y decreased IL-1β release, and Y1 receptor antagonists inhibited IL-1β release and induced epithelial mesenchymal transition in human alveolar epithelial cells. Patients with idiopathic pulmonary fibrosis had lower neuropeptide Y and greater IL-1β levels in the serums compared to healthy controls. Neuropeptide Y expression was mainly observed around bronchial epithelial cells in human idiopathic pulmonary fibrosis lungs. These data suggest that neuropeptide Y plays a protective role against pulmonary fibrosis by suppressing IL-1β release and manipulating the neuropeptide Y-Y1 receptor axis could be a potential therapeutic strategy for delaying disease progression.

DOI： 10.1165/rcmb.2021-0542OC

Idiopathic Plasmacytic Lymphadenopathy Forms an Independent Subtype of Idiopathic Multicentric Castleman Disease Reviewed

Asami Nishikori, Midori Nishimura, Yoshito Nishimura, Fumio Otsuka, Kanna Maehama, Kumiko Ohsawa, Shuji Momose, Naoya Nakamura, Yasuharu Sato

International Journal of Molecular Sciences 23 ( 18 ) 10301 - 10301 2022.9

Authorship：Last author,　Corresponding author Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Idiopathic multicentric Castleman disease (iMCD) is a type of Castleman disease that is not related to KSHV/HHV8 infection. Currently, iMCD is classified into iMCD-TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) and iMCD-NOS (not otherwise specified). The former has been established as a relatively homogeneous disease unit that has been recently re-defined, while the latter is considered to be a heterogeneous disease that could be further divided into several subtypes. In 1980, Mori et al. proposed the concept of idiopathic plasmacytic lymphadenopathy (IPL), a disease presenting with polyclonal hypergammaglobulinemia and a sheet-like proliferation of mature plasma cells in the lymph nodes. Some researchers consider IPL to be a part of iMCD-NOS, although it has not been clearly defined to date. This is the first paper to analyze iMCD-NOS clinicopathologically, to examine whether IPL forms a uniform disease unit in iMCD. Histologically, the IPL group showed prominent plasmacytosis and the hyperplasia of germinal centers, while the non-IPL group showed prominent vascularity. Clinically, the IPL group showed significant thrombocytosis and elevated serum IgG levels compared to the non-IPL group (p = 0.007, p < 0.001, respectively). Pleural effusion and ascites were less common in the IPL group (p < 0.001). The IPL group was more likely to have an indolent clinical course and a good response to the anti-IL-6 receptor antibody, while the non-IPL counterpart frequently required more aggressive medical interventions. Thus, the IPL group is a clinicopathologically uniform entity that forms an independent subtype of iMCD.

DOI： 10.3390/ijms231810301

Clinicopathological characteristics of gastric IgG4-related disease: Systematic scoping review. Reviewed International journal

Haruki Sawada, Torrey Czech, Krixie Silangcruz, Landon Kozai, Adham Obeidat, Eric Andrew Wien, Midori Filiz Nishimura, Asami Nishikori, Yasuharu Sato, Yoshito Nishimura

Journal of gastroenterology and hepatology 2022.8

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

BACKGROUND: Gastric IgG4-related disease (IgG4-RD) can mimic malignancy, submucosal tumors (SMT), and ulcers, leading to over-triage and unnecessary medical interventions such as gastrectomy. The variability in the clinicopathological presentation of IgG4-related disease is not yet well defined, posing a diagnostic challenge. METHODS: Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including"gastritis," "stomach," "gastrointestinal stromal tumor," and "IgG4-RD" from their inception to December 28, 2021. RESULTS: 39 articles, including two observational studies and 42 cases, were included in the systematic review. While bottom-heavy lymphoplasmacytic mucosal infiltration is a characteristic finding of gastric IgG4-RD, it was only present in less than half of the patients in the observational studies. Patients with Gastric IgG4-RD were more likely to be diagnosed with gastrointestinal stromal tumor (GIST), gastric cancer, or peptic ulcer disease and their clinical course involved resection (51.3%) or even gastrectomy. Diagnosis of gastric IgG4-RD was most frequently made by post-operative pathological analysis. CONCLUSION: This systematic review summarizes the current understanding of the characteristics of gastric IgG4-RD. Increased awareness of gastric IgG4-RD as a differential diagnosis of gastric SMT or ulcers among clinicians is crucial in order to reduce unnecessary high-risk, invasive interventions.

DOI： 10.1111/jgh.15980

9p24.1 Genetic Alteration and PD-L1 Expression Are Characteristic of De Novo and Methotrexate-associated Epstein-Barr Virus-positive Hodgkin Lymphoma, But Not Methotrexate-associated Hodgkin-like Lesions. Reviewed International journal

Sawako Shiraiwa, Yara Yukie Kikuti, Joaquim Carreras, Yusuke Kondo, Ken Ohmachi, Yoshiaki Ogawa, Hiroshi Kawada, Shinji Sato, Yuka Gion, Yasuharu Sato, Naoya Nakamura, Kiyoshi Ando

The American journal of surgical pathology 46 ( 8 ) 1017 - 1024 2022.8

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

Although the alteration of the 9p24.1 chromosome locus and PD-L1 overexpression is found in nodular sclerosis classic Hodgkin lymphoma, whether these aberrations occur in CHL and Hodgkin-like lesion (HLL) of methotrexate-associated lymphoproliferative disorder (MTX-CHL and MTX-HLL) is unknown. We compared the clinicopathologic features, the genomic status of the 9p24.1 locus and PD-L1 expression in a series of 34 patients including 17 with Epstein-Barr virus-positive de novo CHL, 7 with MTX-CHL, 10 with MTX-HLL using an immunofluorescence in situ hybridization method and immunohistochemistry. The proportions of cells with 9p24.1 genetic alteration in CD30-positive Hodgkin/Reed-Sternberg cells of de novo CHL, MTX-CHL and MTX-HLL were 55%, 68%, and 24%, respectively. The positive rates of PD-L1 measured by immunohistochemical H-scores of de novo CHL, MTX-CHL and MTX-HLL were 142±38, 157±75, and 70±42, respectively. Alteration of the 9p24.1 gene and expression of PD-L1 protein were correlated with all 3 diseases (correlation coefficient, 0.731). Both alteration of the 9p24.1 gene and overexpression of PD-L1 protein were observed in Epstein-Barr virus-positive de novo CHL and MTX-CHL but not in MTX-HLL. In conclusion, MTX-CHL has similar pathogenesis-like de novo CHL, but MTX-HLL seems to be a different disease from de novo CHL and MTX-CHL.

DOI： 10.1097/PAS.0000000000001899

Global public awareness of Castleman disease and TAFRO syndrome between 2015 and 2021: A Google Trends analysis. Reviewed International journal

Yoshito Nishimura, Midori Filiz Nishimura, David C Fajgenbaum, Frits van Rhee, Yasuharu Sato, Fumio Otsuka

EJHaem 3 ( 3 ) 748 - 753 2022.8

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

Castleman disease (CD) is a rare lymphoproliferative disorder with multiple subtypes. Thrombocytopenia, anasarca, fever, reticulin fibrosis or renal insufficiency, and organomegaly (TAFRO) syndrome can occur in the context of CD. The study evaluated worldwide public awareness of CD and TAFRO syndrome using Google Trends data between 2015 and 2021. Our results showed that global public interest steadily grew until late 2019, at a small but significant rate of 1.1% per month from the 1st to 57th month (1/2015-9/2019). The increase coincided with a peak in the United States and Japan, but the search volume decreased at a rate of 1.3% per month after that time. No clear trend changes were noted throughout the study period with the search term "TAFRO." However, the search volume significantly increased during the time period at a rate of 4.8% (confidence interval [CI]: 2.8, 6.8) and 4.7% (CI: 2.7, 6.8) per month in Japan and worldwide, respectively. There was an insufficient search volume for "TAFRO" in the United States to perform the analysis. Most searches on "TAFRO" stemmed from Japan, suggesting considerable geographical disparity in the awareness of TAFRO syndrome. Further efforts are crucial to raise the awareness of CD and TAFRO syndrome among physicians and the general public, primarily in non-USA and Japanese countries.

DOI： 10.1002/jha2.459

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jha2.459

キャッスルマン病の歴史と病理 Invited Reviewed

佐藤康晴, 錦織亜沙美, 前濱かんな, 西村碧フィリーズ

診断病理 39 ( 3 ) 167 - 172 2022.7

Authorship：Lead author,　Corresponding author Language：Japanese Publisher：(一社)日本病理学会

キャッスルマン病は、リンパ節の病理像で特徴づけられており、いくつかの亜型が存在するヘテロな疾患単位である。原型は限局性で全身症状の乏しい単心性キャッスルマン病(UCD)であったが、その後、病変が多発し全身症状を呈する多中心性キャッスルマン病(MCD)が報告された。MCDはさらにKSHV/HHV8の感染状態によって分類され、陰性例は特発性MCD(iMCD)と定義されている。本項では、キャッスルマン病の歴史を振り返り、各亜型の臨床および病理学的特徴について述べる。(著者抄録)

Clinical characteristics and outcomes of IgG4-positive marginal zone lymphoma: Systematic scoping review. Reviewed International journal

Yoshito Nishimura, Eric Andrew Wien, Midori Filiz Nishimura, Asami Nishikori, Yasuharu Sato, Fumio Otsuka

Pathology international 2022.6

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

Immunoglobulin G4 (IgG4)-positive marginal zone lymphoma (MZL) is rare and undefined. It is unclear whether IgG4-positive MZLs have as favorable an outcome as MZLs in general. Also, correlation with IgG4-related disease (IgG4-RD) and IgG4-positive MZLs is unknown. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including"IgG4" and "marginal zone lymphoma" from their inception to February 20, 2022. Twenty-two articles, including six observational studies and 24 cases from 16 case reports and case series, were included. Only one study had a comparative group, and the other five were exploratory observational studies. IgG4-positive MZLs commonly occurred in males (83.3%). It primarily involved ocular adnexa (41.7%) and skin (29.2%). Only 29.2% had concurrent IgG4-RD, and no expiration was noted. While most cases were treated with excision, resection, or clinical observation, 21.7% received rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone as a first-line treatment. This systematic review summarizes the current understanding of the characteristics of IgG4-positive MZLs. While there seems to be IgG4-RD-related and de novo IgG4-positive MZLs, future research needs to clearly define MZL with polyclonal IgG4-positive cells and IgG4-producing lymphoma. Further studies are critical to clarifying long-term prognosis and optimal surveillance planning.

DOI： 10.1111/pin.13251

Distinct disease-specific Tfh cell populations in two different fibrotic diseases: IgG4-related disease and Kimura's disease. Reviewed International journal

Ryusuke Munemura, Takashi Maehara, Yuka Murakami, Risako Koga, Ryuichi Aoyagi, Naoki Kaneko, Atsushi Doi, Cory A Perugino, Emanuel Della-Torre, Takako Saeki, Yasuharu Sato, Hidetaka Yamamoto, Tamotsu Kiyoshima, John H Stone, Shiv Pillai, Seiji Nakamura

The Journal of allergy and clinical immunology 2022.5

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

BACKGROUND: How T follicular (Tfh) cells contribute to many different B-cell class-switching events during T cell-dependent immune responses has been unclear. Diseases with polarized isotype switching offer a unique opportunity for the exploration of Tfh subsets. Secondary and tertiary lymphoid organs (SLOs and TLOs) in patients with elevated tissue expression levels of IgE (Kimura's disease, KD) and those of IgG4 (IgG4-related disease, IgG4-RD) can provide important insights regarding cytokine expression by Tfh cells. OBJECTIVE: To identify disease-specific Tfh cell subsets in SLOs and TLOs expressing IL-10 or IL-13 and thus identify different cellular drivers of class switching in two distinct types of fibrotic disorders: allergic fibrosis (driven by type 2 immune cells) and inflammatory fibrosis (driven by cytotoxic T lymphocytes). METHODS: Single-cell RNA-sequencing, in situ sequencing, and multi-color immunofluorescence analysis was used to investigate B cells, Tfh cells and infiltrating type 2 cells in lesion tissues from patients with KD or IgG4-RD. RESULTS: Infiltrating Tfh cells in TLOs from IgG4-RD were divided into six main clusters. We encountered abundant infiltrating IL-10-expressing LAG3+ Tfh cells in patients with IgG4-RD. Furthermore, we found that infiltrating AID+CD19+B cells expressing IL-4, IL-10, and IL-21 receptors correlated with IgG4 expression. In contrast, we found that infiltrating IL-13-expressing Tfh cells were abundant in affected tissues from patients with KD. Moreover, we observed few infiltrating IL-13-expressing Tfh cells in tissues from patients with IgG4-RD, despite high serum levels of IgE (but low IgE in the disease lesions). Cytotoxic T cells were abundant in IgG4-RD, and in contrast Type 2 immune cells were abundant in KD. CONCLUSIONS: This single-cell dataset revealed a novel subset of IL10+LAG3+Tfh cells infiltrating the affected organs of IgG4-RD patients. In contrast, IL13+Tfh cells and type 2 immune cells infiltrated those of KD patients.

DOI： 10.1016/j.jaci.2022.03.034

Historical and pathological overview of Castleman disease. Invited Reviewed

Midori Filiz Nishimura, Yoshito Nishimura, Asami Nishikori, Tadashi Yoshino, Yasuharu Sato

Journal of clinical and experimental hematopathology : JCEH 2022.4

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

Castleman disease consists of several lymphoproliferative subtypes that share some histological features in the lymph nodes. On the other hand, numerous clinical findings and etiologies make the disease challenging to understand. The origin of the disease is the hyaline vascular-type unicentric Castleman disease (UCD), first reported by Benjamin Castleman et al. in 1954. Although UCD is characterized by localized lesions and lack of symptoms, multicentric Castleman disease (MCD) with multiple lesions and systemic symptoms was reported by Frizzera in 1983. MCD is further divided according to KSHV/HHV8 infection status. In KSHV/HHV8-related MCD, viral infection signals lead to excessive cytokine production, and cause clinical and pathologic abnormalities. Some cases of plasma cell-type KSHV/HHV8-negative MCD can be found in association with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-proteins, and skin changes), which is a paraneoplastic syndrome. The others are idiopathic MCD, which are currently considered a heterogeneous group of diseases with overlapping pathological and clinical features. In this article, we summarize the historical evolution of Castleman disease to help understand the disease concept. We also review the latest ideas and definitions of the subtypes within the MCD spectrum and summarize the histopathological findings.

DOI： 10.3960/jslrt.21036

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