Faculty Profiles - SATO Yasuharu

Papers - SATO Yasuharu

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Comment on: HHV-8-negative multicentric Castleman disease patients with serological, histopathological and imaging features of IgG4-related disease: reply. Reviewed International journal

Mitsuhiro Kawano, Yasuharu Sato, David C Fajgenbaum

Rheumatology (Oxford, England) 60 ( 2 ) e76-e77 2021.2

Epstein-Barr Virus-Positive Mucocutaneous Ulcer: A Unique and Curious Disease Entity. Reviewed International journal

Tomoka Ikeda, Yuka Gion, Yoshito Nishimura, Midori Filiz Nishimura, Tadashi Yoshino, Yasuharu Sato

International journal of molecular sciences 22 ( 3 ) 2021.1

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

Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) was first described as a lymphoproliferative disorder in 2010. EBVMCU is a unifocal mucosal or cutaneous ulcer that often occurs after local trauma in patients with immunosuppression; the patients generally have a good prognosis. It is histologically characterized by proliferating EBV-positive atypical B cells accompanied by ulcers. On the basis of conventional pathologic criteria, EBVMCU may be misdiagnosed as EBV-positive diffuse large B-cell lymphoma or other lymphomas. However, its prognosis differs from that of EBV-associated lymphomas, in that patients with EBVMCU frequently show spontaneous regression or complete remission without chemotherapy. Therefore, EBVMCU is now recognized as a low-grade malignancy or a pseudo-malignant lesion. Avoiding unnecessary chemotherapy by distinguishing EBVMCU from other EBV-associated lymphomas will reduce the burden and unnecessary harm on patients. On the basis of these facts, EBVMCU was first described as a new clinicopathological entity by the World Health Organization in 2017. In this review, we discuss the clinicopathological characteristics of previously reported EBVMCU cases, while focusing on up-to-date clinical, pathological, and genetic aspects.

DOI： 10.3390/ijms22031053

HHV-8-negative multicentric Castleman disease patients with serological, histopathological and imaging features of IgG4-related disease. Reviewed International journal

Mitsuhiro Kawano, Satoshi Hara, Akihiro Yachie, Dai Inoue, Yasuharu Sato, David C Fajgenbaum

Rheumatology (Oxford, England) 60 ( 1 ) e3-e4 2021.1

Follow-up with serum IgG4-monitoring in 8 patients with IgG4-related disease diagnosed by a lacrimal gland mass. Reviewed

Toshihiko Matsuo, Takehiro Tanaka, Yasuharu Sato, Hitomi Kataoka, Mayu Uka, Daisuke Ennishi, Tomofumi Yano

Journal of clinical and experimental hematopathology : JCEH 61 ( 1 ) 10 - 21 2021

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

The diagnostic criteria for IgG4-related disease were previously published and serum IgG4 measurement has been reimbursed by national health insurance in Japan since 2012. Eight patients diagnosed with IgG4-related disease based on lacrimal gland masses were retrospectively reviewed. The 8 patients were 3 men and 5 women ranging in age from 52 to 77 (median, 63) years at the initial visit and their follow-up period ranged from 0.25 to 11 (median, 7) years. Bilateral and unilateral involvement were noted in 4 patients each; 2 on the right side and 2 on the left side in those with unilateral involvement. Serum IgG4 was high in 5 of 8 patients at the initial visit. Five patients with no systemic signs were followed without treatment, whereas oral steroids were administered and tapered in the other 3 patients who exhibited systemic signs. One patient with a history of radiation for MALT lymphoma in bilateral lacrimal glands developed IgG4-related disease in the left lacrimal gland 10 years later and was followed without treatment. Nine years later, her serum IgG4 level increased to 1500 mg/dL and paracardiac lesions, found on positron emission tomography, were confirmed to be MALT lymphoma by needle biopsy, leading to systemic chemotherapy. The other 7 patients had neither local recurrence nor additional systemic signs. Serum IgG4 monitoring may be useful to detect systemic complications in IgG4-related ophthalmic disease and markedly high serum IgG4 levels may indicate new lymphoma at other sites.

DOI： 10.3960/jslrt.20048

IgG4 Expression in Patients with Eosinophilic Otitis Media Reviewed

Masahiro Takahashi, Aiko Oka, Shin Kariya, Yuka Gion, Yasuharu Sato, Satoshi Iwasaki, Shogo Oyamada, Atsushi Matsubara, Mitsuhiro Okano

ORL 83 ( 3 ) 167 - 171 2021

Publishing type：Research paper (scientific journal) Publisher：S. Karger AG

<b><i>Objective:</i></b> Eosinophilic otitis media (EOM) is an intractable middle ear disease recognized by an eosinophil enriched middle ear effusion and mucosa. Although precise pathogenesis of EOM remains unclear, it is characterized by type 2 inflammation. Since IgG4 is an IgG subclass induced by type 2 cytokines such as IL-4 and IL-13, we sought to characterize and compare local IgG4 expression in patients with and without EOM. <b><i>Methods:</i></b> Twelve patients with bilateral profound hearing loss, 9 of which underwent a cochlear implant surgery, were enrolled in this study (6 with EOM and 6 without EOM). The surgical specimens were harvested during surgery and were subjected to IgG4 immunostaining. <b><i>Result:</i></b> The middle ear mucosa showed the presence of a large number of IgG4-positive cells in patients with EOM, which was significantly higher than that in patients without EOM. <b><i>Conclusion:</i></b> Local IgG4 expression was observed in patients with EOM in comparison to those without EOM, suggesting that IgG4 contributes to EOM pathogenesis.

DOI： 10.1159/000512726

Differential diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma and other indolent lymphomas, including mantle cell lymphoma. Reviewed

Tadashi Yoshino, Takehiro Tanaka, Yasuharu Sato

Journal of clinical and experimental hematopathology : JCEH 60 ( 4 ) 124 - 129 2020.12

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

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) accounts for approximately 1% of all lymphomas in our department. In this article, we describe the differential diagnosis of CLL/SLL from other indolent lymphomas, with special reference to follicular lymphoma, marginal zone B-cell lymphoma, lymphoplasmacytic lymphoma, and mantle cell lymphoma, although the latter is considered to be aggressive. CLL/SLL often exhibits proliferation centers, similar to follicular lymphoma. Immunohistological examination can easily distinguish these two lymphomas. The most important characteristic of CLL/SLL is CD5 and CD23 positivity. Mantle cell lymphoma is also CD5-positive and there are some CD23-positive cases. Such cases should be carefully distinguished from CLL/SLL. Some marginal zone lymphomas are also positive for CD5 and such cases are often disseminated. Lymphoplasmacytic lymphoma should also be a differential diagnosis for CLL/SLL. It frequently demonstrates MYD88 L265P, which is a key differential finding. By immunohistological examination, the expression of lymphoid enhancer-binding factor 1 is specific for CLL/SLL and can be a good marker in the differential diagnosis.

DOI： 10.3960/jslrt.19041

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

Authorship：Last author,　Corresponding author 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

Clinicopathological analysis of 34 Japanese patients with EBV-positive mucocutaneous ulcer. Reviewed International journal

Tomoka Ikeda, Yuka Gion, Misa Sakamoto, Tomoyasu Tachibana, Asami Nishikori, Midori Filiz Nishimura, Tadashi Yoshino, Yasuharu Sato

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 33 ( 12 ) 2437 - 2448 2020.12

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

Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a unifocal mucosal or cutaneous ulcer that is histologically characterized by proliferating EBV-positive atypical B cells. While EBVMCU demonstrates a histology similar to that of EBV-positive diffuse large B-cell lymphoma (DLBCL), their clinical behavior differs. Thus, characterizing distinguishing features of EBVMCU and EBV-positive DLBCL is critical. To identify unique characteristics between EBVMCU and lymphoma, we analyzed the clinicopathological and genetic features of 34 Japanese patients with EBVMCU and compared them to those of 24 EBV-positive DLBCL patients and 25 EBV-negative DLBCL patients. All patients with EBVMCU had localized ulcerative lesions, and 31 patients (91%) were using immunosuppressants, such as methotrexate (MTX) or hydroxycarbamide. All patients that were followed up with exhibited good prognosis following immunosuppressant reduction or chemotherapy. In addition, 17 EBV-positive DLBCL patients, and 15 EBV-negative DLBCL patients, received chemotherapy (P < 0.001, P < 0.001, respectively). Our data showed that EBVMCU did not increase indicators associated with lymphoma prognosis, such as soluble interleukin 2 receptor (sIL-2R) and lactate dehydrogenase (LDH) compared to those in the EBV-positive DLBCL or EBV-negative DLBCL groups (sIL-2R, P < 0.001, P = 0.025; LDH, P = 0.018, P = 0.038, respectively). However, histologically, EBVMCU exhibited EBV-positive, variable-sized, atypical B-cell proliferation. Thus, EBVMCU was histologically classified as: (1) polymorphous; (2) large cell-rich; (3) classic Hodgkin lymphoma-like; and (4) mucosa-associated lymphoid tissue lymphoma-like. Moreover, genetic analysis showed that immunoglobin heavy chain (IGH) gene rearrangement did not differ significantly between EBVMCU and EBV-positive DLBCL (44% vs. 32%; P = 0.377), or between EBVMCU and EBV-negative DLBCL (44% vs. 58%; P = 0.280). Therefore, it is difficult to distinguish EBVMCU from EBV-positive DLBCL using only pathological and genetic findings, suggesting that clinical information is important in accurately distinguishing between EBVMCU and EBV-positive DLBCL.

DOI： 10.1038/s41379-020-0599-8

Treatment outcomes of IgG4-producing marginal zone B-cell lymphoma: a retrospective case series. Reviewed

Yuichi Sumii, Noboru Asada, Yasuharu Sato, Koh-Ichi Ohshima, Masanori Makita, Yusuke Yoshimoto, Yuka Sogabe, Kenji Imajo, Yusuke Meguri, Daisuke Ennishi, Hisakazu Nishimori, Nobuharu Fujii, Ken-Ichi Matsuoka, Tadashi Yoshino, Yoshinobu Maeda

International journal of hematology 112 ( 6 ) 780 - 786 2020.12

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

IgG4-producing marginal zone B-cell lymphomas (MZLs) have been recently proposed as a subtype of MZLs. Despite the abundant literature on pathophysiological features of this type of lymphoma, only a few retrospective studies pertaining to the treatment outcomes have been reported, and its prognosis remains unclear. We retrospectively analyzed seven patients with IgG4-producing MZLs diagnosed at our institute, with specific reference to treatment and outcomes. The median age was 69.0 years (55-79), and all were males. The median follow-up period was 66.6 months (8-121). All patients had localized disease; four patients had tumors of the ocular adnexa, whereas two had retroperitoneal tumors. Five patients were treated with irradiation (30 Gy/15 fr) (n = 4) or surgery (n = 1), resulting in tumor reduction. Two patients were treated by chemotherapy or irradiation. Among them, one commenced rituximab monotherapy, which led to an inadequate reduction of the tumor. Subsequent irradiation induced complete response (CR). The other patient experienced repeated relapses during follow-up and finally achieved CR by combination chemotherapy. Treatment was well tolerated in all cases, and none of the patients showed disease progression at the last follow-up visit. Our results indicate that the standard treatments for MZLs are generally appropriate for IgG4-producing MZL.

DOI： 10.1007/s12185-020-02968-w

Insufficient evidence exists to use histopathologic subtype to guide treatment of idiopathic multicentric Castleman disease. Reviewed International journal

David C Fajgenbaum, David Wu, Aaron Goodman, Raymond Wong, Amy Chadburn, Sunita Nasta, Gordan Srkalovic, Sudipto Mukherjee, Heather Leitch, Raj Jayanthan, Simone Ferrero, Yasuharu Sato, Steve Schey, Angela Dispenzieri, Eric Oksenhendler, Pier Luigi Zinzani, Mary Jo Lechowicz, Christian Hoffmann, Naveen Pemmaraju, Adam Bagg, Alexander Fossa, Megan S Lim, Frits van Rhee

American journal of hematology 95 ( 12 ) 1553 - 1561 2020.12

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

Idiopathic multicentric Castleman disease (iMCD) is a rare immunologic disorder characterized by systemic inflammation, multicentric lymphadenopathy, and organ dysfunction. Enlarged lymph nodes demonstrate a spectrum of characteristic but variable histopathologic features historically categorized into hyaline vascular (HV) (or hypervascular [HyperV] more recently), plasmacytic, or "mixed." Though the etiology is unknown, a pro-inflammatory cytokine storm, often involving interleukin-6 (IL-6), contributes to pathogenesis. Anti-IL-6 therapy with siltuximab is the only FDA- or EMA-approved treatment based on efficacy and safety in multiple studies. Importantly, no patients considered to have HV histopathology achieved the primary endpoint in the Phase II study. NCCN currently recommends siltuximab first-line for iMCD, except for patients considered to have HV histopathology. We investigated whether histopathologic subtype should guide siltuximab treatment decisions. Secondary analyses of clinical trial and real-world data revealed similar clinical benefit across histopathologic subtypes. Notably, only 18 of 79 patients in the Phase II study were consistently classified into histopathologic subtype by three independent review panels, demonstrating limited reliability to guide treatment decisions. Real-world data further demonstrate siltuximab's effectiveness in patients considered to have HV (or HyperV). Though histopathology is a critical component for diagnosis, there is insufficient evidence to guide treatment based solely on lymph node histopathologic subtype.

DOI： 10.1002/ajh.25992

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

Methotrexate-Associated Lymphoproliferative Disorders Mimicking Granulomatosis With Polyangiitis: A Radiological Diagnostic Challenge. Reviewed International journal

Tomoyasu Tachibana, Tomoaki Sasaki, Yoji Wani, Yasutoshi Komatsubara, Kazunori Kuroda, Yuto Naoi, Yuka Gion, Yorihisa Orita, Kazunori Nishizaki, Yasuharu Sato

Ear, nose, & throat journal 101 ( 8 ) 145561320970685 - 145561320970685 2020.11

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

Methotrexate-associated lymphoproliferative disorders (MTX-LPD) frequently involve the extranodal organs throughout the body. Among the extranodal occurrences of MTX-LPD, pulmonary involvement is most frequent. In contrast, there are only a few reports of MTX-LPD in the nasal cavity or paranasal sinuses. Moreover, there are no previous reports of MTX-LPD mimicking granulomatosis with polyangiitis (GPA) in imaging examinations. We describe a case of a 53-year-old woman with MTX-LPD mimicking GPA in the nasal cavity and lungs. She complained of left nasal obstruction and discharge, general fatigue, and continual fever for 2 months. The patient had been diagnosed with rheumatoid arthritis and received methotrexate (MTX) for over 10 years. Contrast-enhanced computed tomography revealed unenhanced masses in the nasal cavity and multiple masses with cavitary changes in the bilateral lungs, suggesting GPA. However, histological examination of the nasal lesion and a history of MTX treatment indicated a diffuse large B-cell lymphoma type MTX-LPD. Two weeks after MTX withdrawal, prominent improvements in both lesions were observed. Complete regression of the nasal lesion was observed 3 months after discontinuation of MTX. Thus, MTX-LPD may mimic GPA in imaging examinations.

DOI： 10.1177/0145561320970685

Application of Lip Biopsy for the Histological Diagnosis of Immunoglobulin G4-Related Disease. Reviewed International journal

Tomoyasu Tachibana, Yorihisa Orita, Yoji Wani, Yasutoshi Komatsubara, Kazunori Kuroda, Yuto Naoi, Yuka Gion, Takuma Makino, Kazunori Nishizaki, Yasuharu Sato

Ear, nose, & throat journal 101 ( 8 ) 145561320971932 - 145561320971932 2020.11

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

We describe the case of a 51-year-old woman with immunoglobulin G4-related disease (IgG4-RD) diagnosed using lip biopsy. She reported having bilateral submandibular nodules for a month. Magnetic resonance imaging showed diffuse swelling in the bilateral submandibular glands (SMGs), suggesting inflammatory changes. Laboratory data revealed an elevated level of serum IgG4. Fine needle aspiration cytology of the SMG showed a considerable number of lymphocytes with degeneration but did not demonstrate specific findings for a definitive diagnosis of IgG4-RD. Lip biopsy was performed, and a biopsy specimen from the labial salivary gland showed abundant lymphoplasmacytic infiltration with a large number of IgG4-positive cells. The patient was diagnosed with IgG4-RD based on histological and laboratory findings. Findings of further examinations revealed that the patient had autoimmune pancreatitis, confirming our diagnosis. Four months after prednisolone administration, improvement of the submandibular and pancreatic lesions was observed. One year after the initial presentation, the serum IgG4 level was normalized. In cases of IgG4-RD with salivary gland involvement, lip biopsy might be one of the options for the histological diagnosis of IgG4-RD.

DOI： 10.1177/0145561320971932

A Novel Predictive Model for Idiopathic Multicentric Castleman Disease: The International Castleman Disease Consortium Study. Reviewed International journal

Li Yu, Menghan Shi, Qingqing Cai, Paolo Strati, Fredrick Hagemeister, Qiongli Zhai, Ling Li, Xiaosheng Fang, Jianyong Li, Ruifang Sun, Shanxiang Zhang, Hanjin Yang, Zhaoming Wang, Wenbin Qian, Noriko Iwaki, Yasuharu Sato, Lu Zhang, Jian Li, Eric Oksenhendler, Zijun Y Xu-Monette, Ken H Young

The oncologist 25 ( 11 ) 963 - 973 2020.11

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

BACKGROUND: Patients with multicentric Castleman disease (MCD) who are negative for human immunodeficiency virus and human herpesvirus 8 are considered to have idiopathic MCD (iMCD). The clinical presentation of iMCD varies from mild constitutional symptoms to life-threatening symptoms or death. The treatment strategy varies from "watchful waiting" to high-dose chemotherapy. This diverse clinical presentation calls for a classification stratification system that takes into account the severity of the disease. SUBJECTS, MATERIALS, AND METHODS: We analyzed the clinical, laboratory, and pathologic abnormalities and treatment outcomes of 176 patients with iMCD (median follow-up duration 12 years) from the U.S. and China to better understand the characteristics and prognostic factors of this disease. This discovery set of iMCD results was confirmed from the validation set composed of additional 197 patients with iMCD organized from The International Castleman Disease Consortium. RESULTS: Using these data, we proposed and validated the iMCD international prognostic index (iMCD-IPI), which includes parameters related to patient characteristics (age > 40 years), histopathologic features (plasma cell variant), and inflammatory consequences of iMCD (hepatomegaly and/or splenomegaly, hemoglobin <80 g/L, and pleural effusion). These five factors stratified patients according to their performance status and extent of organ dysfunction into three broad categories: low risk, intermediate risk, and high risk. The iMCD-IPI score accurately predicted outcomes in the discovery study cohort, and the results were confirmed on the validation study cohort. CONCLUSION: This study represents the largest series of studies on patients with iMCD in the field and proposed a novel risk-stratification model for iMCD-IPI that could be used to guide risk-stratified treatment strategies in patients with iMCD. IMPLICATIONS FOR PRACTICE: Patients with idiopathic multicentric Castleman disease (iMCD) can benefit from care based on clinical symptoms and disease severity. This study in 176 patients with iMCD constructed an iMCD-IPI score based on five clinical factors, including age >40 years, plasmacytic variant subtype, hepatomegaly and/or splenomegaly, hemoglobin <80 g/L, and pleural effusion, and stratified patients into three risk categories: low risk, intermediate risk, and high risk. The predictive value was validated in an independent set of 197 patients with iMCD from The International Castleman Disease Consortium. The proposed novel model is valuable for predicting clinical outcome and selecting optimal therapies using clinical parameters.

DOI： 10.1634/theoncologist.2019-0986

Pathological evaluation of radiotherapy and concomitant intraarterial cisplatin for maxillary sinus cancer. Reviewed International journal

Takuma Makino, Tomoyasu Tachibana, Shin Kariya, Yusuke Matsui, Hidenobu Matsuzaki, Shohei Fujimoto, Yorihisa Orita, Kuniaki Katsui, Takao Hiraki, Yasuharu Sato, Susumu Kanazawa, Kazunori Nishizaki

Auris, nasus, larynx 47 ( 5 ) 881 - 886 2020.10

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

OBJECTIVE: Since 2010, we have mainly performed surgical treatment following radiotherapy and concomitant intraarterial cisplatin (RADPLAT) for locally advanced maxillary sinus cancer (MSC). The present study investigated treatment results and pathological evaluations following RADPLAT for MSC. METHODS: Pathological response to RADPLAT was evaluated using surgical specimens. Pathological response was graded in accordance with the classification method that Shimosato reported in 1964, as grade V (no tumor cells remain in any of section), grade IV, III, II, I, and 0. Five-year overall and disease-specific survival rates were estimated using Kaplan-Meier methods. Univariate analyses of correlations between recurrence of MSC and other clinicopathological parameters were evaluated using the chi-square or Fisher's exact tests. RESULT: 19 patients were enrolled in this study, 5 patients showed T3 disease and 14 had T4 disease. One patient demonstrated local recurrence and 3 patients experienced distant metastasis. The 5-year overall survival rate was 67.1% (T3, 50.0%; T4, 69.6%), and the 5-year disease-specific survival rate was 81.9% (T3, 100%; T4, 76.0%). Histological response was categorized as grade V in 9 cases. No significant risk factors for residual cancer were identified. CONCLUSION: Our study suggested that RADPLAT not only has a low risk of side effects, but also could represent an effective procedure for locally advanced MSC by pathological evaluation. Increasing the therapeutic intensity of RADPLAT might provide an effective modality to avoid highly invasive surgery.

DOI： 10.1016/j.anl.2020.04.004

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

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

Primary human herpesvirus 8-negative effusion-based lymphoma: a large B-cell lymphoma with favorable prognosis. Reviewed International journal

Daisuke Kaji, Yasunori Ota, Yasuharu Sato, Koji Nagafuji, Yasunori Ueda, Masataka Okamoto, Yasushi Terasaki, Naoko Tsuyama, Kosei Matsue, Tomohiro Kinoshita, Go Yamamoto, Shuichi Taniguchi, Shigeru Chiba, Koichi Ohshima, Koji Izutsu

Blood advances 4 ( 18 ) 4442 - 4450 2020.9

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

Primary effusion-based lymphoma (EBL) presents as a malignant effusion in a body cavity. The clinicopathologic features and prognosis of primary human herpesvirus 8 (HHV8)-negative EBL remain unclear. We therefore conducted a retrospective study of 95 patients with EBL, regardless of HHV8 status, in Japan. Of 69 patients with EBL tested for HHV8, a total of 64 were negative. The median age of patients with primary HHV8-negative EBL at diagnosis was 77 years (range, 57-98 years); all 58 tested patients were negative for HIV. Primary HHV8-negative EBL was most commonly diagnosed in pleural effusion (77%). Expression of at least 1 pan B-cell antigen (CD19, CD20, or CD79a) was observed in all cases. According to the Hans algorithm, 30 of the 38 evaluated patients had nongerminal center B-cell (non-GCB) tumors. Epstein-Barr virus-encoded small RNA was positive in 6 of 45 patients. In 56 of 64 HHV8-negative patients, systemic therapy was initiated within 3 months after diagnosis. Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) or CHOP-like regimens with or without rituximab (n = 48) were the most common primary treatments. The overall response and complete response rates were 95% and 73%, respectively. Three patients did not progress without systemic treatment for a median of 24 months. With a median 25-month follow-up, the 2-year overall survival and progression-free survival rates were 84.7% and 73.8%. Sixteen patients died; 12 were lymphoma-related deaths. Thus, most EBL cases in Japan are HHV8-negative and affect elderly patients. The non-GCB subtype is predominant. Overall, primary HHV8-negative EBL exhibits a favorable prognosis after anthracycline-based chemotherapy.

DOI： 10.1182/bloodadvances.2020002293

Clinical characteristics of subglottic cancer: emphasis on therapeutic management strategies for stage II subglottic cancer. Reviewed International journal

Yasutoshi Komatsubara, Tomoyasu Tachibana, Yorihisa Orita, Takuma Makino, Kazunori Kuroda, Yuto Naoi, Yuko Kataoka, Yasuharu Sato, Shin Kariya, Kazunori Nishizaki

Acta oto-laryngologica 140 ( 9 ) 773 - 778 2020.9

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

Background: Subglottic cancer (SGC) is extremely rare, as most laryngeal cancers are localized to the glottic region. Accordingly, the clinical characteristics of SGC have not been well characterized.Objectives: In the current study, SGCs were clinically evaluated, and the outcomes of radiotherapy (RT) in patients with stage II SGC were assessed.Materials and Methods: Medical data derived from 11 patients with SGC, who were treated at our hospital between 1995 and 2019, were retrospectively reviewed.Results: In our department SGC accounted for 3.9% of the 280 laryngeal cancer patients treated during the study period. At the time of SGC diagnosis, 9 (81.8%) had stage II cancer, 1 had stage III cancer, and 1 had stage IV cancer. Stage II SGC patients treated with concurrent chemoradiotherapy (CCRT) showed a significantly higher local control rate (p = .026) and laryngeal dysfunction free rate (p = .026) than those treated with RT alone. Salvage surgery, performed in 4 patients whose disease was not locally controlled with CCRT/RT, was successful in 3 patients.Conclusion: As a treatment strategy for stage II SGC, CCRT is an acceptable initial treatment for laryngeal function and preservation while salvage surgery is effective for recurrence after CCRT/RT treatment.

DOI： 10.1080/00016489.2020.1767303

Clinicopathologic analysis of gastric mucosa-associated lymphoid tissue lymphoma with or without c-Met expression. Reviewed

Rika Omote, Yuka Gion, Shizuma Omote, Akira Tari, Takehiro Tanaka, Asami Nishikori, Tadashi Yoshino, Yasuharu Sato

Medical molecular morphology 53 ( 3 ) 149 - 155 2020.9

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

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach is mainly associated with Helicobacter pylori infection, and H. pylori eradication therapy is often effective. However, 20-30% of the cases of MALT lymphoma are resistant to the eradication therapy, and translocation of the API2-MALT1 gene is often found in these cases. Most cases without translocation of API2-MALT1 are localized to the stomach, whereas some cases with this translocation are a more advanced stage of MALT lymphoma that spreads to other organs. The c-Met receptor is a prognostic factor involved in infiltration and metastasis in many malignant tumors, including gastric, pancreatic, lung, and kidney cancer. In the present study, the expression of c-Met in 43 cases of gastric MALT lymphomas was immunohistochemically examined and compared with clinicopathological factors. To elucidate the significance of c-Met in MALT lymphoma, the expression intensity of c-Met in 22 API2-MALT1 translocation-positive and 21 API2-MALT1 translocation-negative cases was scored, compared, and examined. The immunohistochemistry analysis revealed strong staining for c-Met in 21 API2-MALT1 translocation-positive cases and in 1 translocation-negative case (P = 0.00). This result indicates the relationship between strong expression of c-Met and the progression of MALT lymphoma with API2-MALT1 gene translocation.

DOI： 10.1007/s00795-019-00241-6

Comparison of the Hybrid Capture II Method with a PCR-Based Screening Method Using a Carboxyfluorescein-Labeled Primer for Detecting Human Papillomavirus in Cervicovaginal Liquid-Based Cytology Reviewed

Yusuke Saiki, Yuka Gion, Asami Nishikori, Yoshiaki Norimatsu, Yasuharu Sato

Journal of Molecular Pathology 1 ( 1 ) 9 - 18 2020.9

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

Objective: Human papillomaviruses (HPVs) are DNA viruses, of which over 120 types have been identified. The main screening methods for HPV-DNA include the hybrid capture II (HC-II) and polymerase chain reaction (PCR) assays. Liquid-based cytology (LBC) is a high-quality technique developed to improve the diagnostic reliability of traditional Papanicolaou tests (Pap tests). However, relatively few studies have compared the efficacy of PCR and HC-II assays using cervicovaginal LBC specimens. In this study, we conducted a comparative analysis with results derived from the HC-II assay to assess whether a PCR-based assay using a novel carboxyfluorescein (FAM)-labeled primer could be applied to cervicovaginal LBC specimens. Methods and Results: We analyzed 59 specimens diagnosed as atypical squamous cells of undetermined significance (ASCUS) by Pap tests. After extracting DNA from cervicovaginal LBC specimens, we performed PCR using a FAM-labeled consensus primer, and then conducted fragment analysis to confirm the results. The value of the kappa statistic measuring the agreement between the PCR and HC-II results was 0.8557, or “almost perfect agreement.” Conclusion: Our novel HPV-PCR assay can be successfully applied to cervicovaginal LBC specimens for the detection of HPV subtypes.

DOI： 10.3390/jmp1010003

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