Faculty Profiles - Nishimura Midori Filiz

Papers - Nishimura Midori Filiz

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Ectopic Breast Cancer Arising within an Axillary Lymph Node. Reviewed

Kei Toshima, Tadahiko Shien, Midori Filiz Nishimura, Yoko Suzuki, Shogo Nakamoto, Maya Uno, Ryo Yoshioka, Takahiro Tsukioki, Yuko Takahashi, Takayuki Iwamoto, Tsuguo Iwatani, Hiroyuki Yanai

Acta medica Okayama 78 ( 1 ) 89 - 93 2024.2

Language：English

We report our experience with the diagnosis and treatment of an ectopic breast cancer arising within an axillary lymph node. The patient was a 65-year-old woman diagnosed breast cancer and axillary lymph node metastasis. We performed a partial mastectomy and axillary lymph node dissection. Postoperative pathology revealed no malignant lesions in the breast; however, a nodule in one of axillary lymph nodes had mixed benign and malignant components, leading to a diagnosis of invasive ductal carcinoma derived from ectopic mammary tissue. This case represents a very rare form of breast cancer, and the malignancy was difficult to distinguish from metastasis.

DOI： 10.18926/AMO/66676

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Analysis of Notch1 protein expression in methotrexate-associated lymphoproliferative disorders Reviewed

Okatani Takeshi, Nishimura Midori Filiz, Egusa Yuria, Yoshida Sayako, Nishimura Yoshito, Nishikori Asami, Yoshino Tadashi, Yamamoto Hidetaka, Sato Yasuharu

Journal of Clinical and Experimental Hematopathology 64 ( 1 ) 1 - 9 2024

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：The Japanese Society for Lymphoreticular Tissue Research

Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a lymphoproliferative disorder in patients treated with MTX. The mechanism of pathogenesis is still elusive, but it is thought to be a complex interplay of factors, such as underlying autoimmune disease activity, MTX use, Epstein-Barr virus infection, and aging. The NOTCH genes encode receptors for a signaling pathway that regulates various fundamental cellular processes, such as proliferation and differentiation during embryonic development. Mutations of NOTCH1 have been reported in B-cell tumors, including chronic lymphocytic leukemia/lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma (DLBCL). Recently, it has also been reported that NOTCH1 mutations are found in post-transplant lymphoproliferative disorders, and in CD20-positive cells in angioimmunoblastic T-cell lymphoma, which might be associated with lymphomagenesis in immunodeficiency. In this study, to investigate the association of NOTCH1 in the pathogenesis of MTX-LPD, we evaluated protein expression of Notch1 in nuclei immunohistochemically in MTX-LPD cases [histologically DLBCL-type (n = 24) and classical Hodgkin lymphoma (CHL)-type (n = 24)] and de novo lymphoma cases [DLBCL (n = 19) and CHL (n = 15)]. The results showed that among MTX-LPD cases, the expression of Notch1 protein was significantly higher in the DLBCL type than in the CHL type (P < 0.001). In addition, among DLBCL morphology cases, expression of Notch1 tended to be higher in MTX-LPD than in the de novo group; however this difference was not significant (P = 0.0605). The results showed that NOTCH1 may be involved in the proliferation and tumorigenesis of B cells under the use of MTX. Further research, including genetic studies, is necessary.

DOI： 10.3960/jslrt.23038

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Other Link： https://www.jstage.jst.go.jp/article/jslrt/64/1/64_23038/_pdf

Multiple Glomus tumor that developed in the lower leg of one side: A case report Reviewed

Takahiro Tokuda, Tomohiro Fujiwara, Ayana Kondo, Toshiyuki Kunisada, Eiji Nakata, Midori Filiz Nishimura, Hiroyuki Yanai, Toshihumi Ozaki

The Journal of the Chugoku-Shikoku Orthopaedic Association 35 ( 1 ) 47 - 51 2023.7

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 Advance online publication 2023.2

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

Asami Nishikori, Midori Filiz 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：Corresponding author Language：English 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

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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

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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

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

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

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

eJHaem 3 ( 3 ) 748 - 753 2022.4

International definition of iMCD-TAFRO: future perspectives. Invited Reviewed

Yoshito Nishimura, Midori Filiz Nishimura, Yasuharu Sato

Journal of clinical and experimental hematopathology : JCEH 2022.4

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

Since thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly (TAFRO) syndrome was first proposed in 2010, there has been considerable progress in this area, particularly regarding its association with idiopathic multicentric Castleman disease (iMCD). TAFRO syndrome is a heterogeneous category with a constellation of symptoms that can develop in the setting of infection, rheumatologic disorder, malignancy, and iMCD. Now, iMCD with TAFRO symptoms is subtyped as iMCD-TAFRO. However, confusion between TAFRO syndrome and iMCD-TAFRO remains. In this article, we discuss the current understanding and future research agenda of TAFRO syndrome and iMCD-TAFRO from the perspective of its new validated international definition.

DOI： 10.3960/jslrt.21037

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Idiopathic multicentric Castleman disease with positive antiphospholipid antibody: atypical and undiagnosed autoimmune disease? Reviewed

Yoshito Nishimura, Asami Nishikori, Haruki Sawada, Torrey Czech, Yuki Otsuka, Midori Filiz Nishimura, Hiroki Mizuno, Naoki Sawa, Shuji Momose, Kumiko Ohsawa, Fumio Otsuka, Yasuharu Sato

Journal of Clinical and Experimental Hematopathology 2022

Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Society for Lymphoreticular Tissue Research

Idiopathic multicentric Castleman disease (iMCD) is a systemic disorder characterized by systemic inflammation and organ dysfunction associated with an increase in pro-inflammatory cytokines. Some patients with iMCD are positive for autoantibodies, although their significance and relationship with specific associated autoimmune diseases are unclear. This study retrospectively analyzed the clinicopathological features of iMCD patients focusing on autoantibodies. Among 63 iMCD patients in our database, 19 were positive for at least one autoantibody. Among the 19, we identified five with plasma cell type (PC)-iMCD lymph node histopathology and positive anti-phospholipid antibodies. These patients were likely to have thrombocytopenia, anasarca, fever, reticulin fibrosis or renal insufficiency, organomegaly (TAFRO) symptoms, and thrombotic events. The present study suggests that patients with undiagnosed or atypical autoimmune diseases, including anti-phospholipid syndrome (APS), were treated for iMCD. APS may present with thrombocytopenia or even multi-organ failure, which overlap with clinical presentations of iMCD. Due to differences in the treatment regimen and follow-up, recognition of the undiagnosed autoimmune disease process in those suspected of iMCD is essential. Our study highlights the importance of complete exclusion of differential diagnoses in patients with iMCD in their diagnostic workup.

DOI： 10.3960/jslrt.21038

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Cytopathological Findings of Secretory Carcinoma of the Salivary Gland and the Diagnostic Utility of Giemsa Staining Reviewed International journal

Yuria Egusa, Midori Filiz Nishimura, Satoko Baba, Kengo Takeuchi, Takuma Makino, Tomoyasu Tachibana, Asami Nishikori, Azusa Fujita, Hiroyuki Yanai, Yasuharu Sato

Diagnostics 11 ( 12 ) 2284 - 2284 2021.12

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

Secretory carcinoma is a salivary gland neoplasm first described as a mammary analogue secretory carcinoma by Skalova et al. in 2010 and redesignated as a secretory carcinoma in the 2017 World Health Organization Classification of Head and Neck Tumors. Secretory carcinoma diagnosis is reliant on specific cytological and histological findings and the detection of an ETV6-NTRK3 fusion gene. Here, we examined the clinical and cytopathological features of four cases of secretory carcinoma occurring in three males and a female, aged between 39 and 74 years. All four tumors involved the parotid gland, and were found to have the ETV6-NTRK3 fusion gene. Fine-needle aspiration-based cytology smears of all tumors displayed papillary and/or dendritic pattern clusters, some of which were associated with blood vessels. The neoplastic cells displayed enlarged nuclei with fine chromatin and small, distinct, single nucleoli. Furthermore, several neoplastic cells with a characteristic vacuolated cytoplasm were identified in each specimen. Giemsa staining revealed cytoplasmic vacuolation, intracytoplasmic metachromatic secretions and/or various sized metachromatic granules, and a background of metachromatic mucin in all four specimens. Given this, we conclude that these cytological findings, especially those of the Giemsa staining, might be helpful in the diagnosis of secretory carcinoma.

DOI： 10.3390/diagnostics11122284

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PD‐L1 expression is associated with the spontaneous regression of patients with methotrexate‐associated lymphoproliferative disorders Reviewed

Yuka Gion, Misato Doi, Yoshito Nishimura, Tomoka Ikeda, Midori Filiz Nishimura, Misa Sakamoto, Yuria Egusa, Asami Nishikori, Azusa Fujita, Noriko Iwaki, Naoya Nakamura, Tadashi Yoshino, Yasuharu Sato

Cancer Medicine 2021.11

Investigation of IgG4‐positive cells in idiopathic multicentric Castleman disease and validation of the 2020 exclusion criteria for IgG4‐related disease Reviewed

Asami Nishikori, Midori Filiz Nishimura, Yoshito Nishimura, Kenji Notohara, Akira Satou, Masafumi Moriyama, Seiji Nakamura, Yasuharu Sato

Pathology International 2021.11

Epstein-Barr virus-positive mucocutaneous ulcer is characterized by relatively low serum soluble IL-2 receptor levels regardless of methotrexate use; Reply to Ramia de Cap and Michaels Reviewed

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

Modern Pathology 2021.8

Upregulated Expression of Activation-Induced Cytidine Deaminase in Ocular Adnexal Marginal Zone Lymphoma with IgG4-Positive Cells Reviewed International journal

Asami Nishikori, Yoshito Nishimura, Rei Shibata, Koh-ichi Ohshima, Yuka Gion, Tomoka Ikeda, Midori Filiz Nishimura, Tadashi Yoshino, Yasuharu Sato

International Journal of Molecular Sciences 22 ( 8 ) 2021.4

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

Immunoglobulin G4-related disease (IgG4-RD) is a systemic disorder characterized by tissue fibrosis and intense lymphoplasmacytic infiltration, causing progressive organ dysfunction. Activation-induced cytidine deaminase (AID), a deaminase normally expressed in activated B-cells in germinal centers, edits ribonucleotides to induce somatic hypermutation and class switching of immunoglobulin. While AID expression is strictly controlled under physiological conditions, chronic inflammation has been noted to induce its upregulation to propel oncogenesis. We examined AID expression in IgG4-related ophthalmic disease (IgG4-ROD; n = 16), marginal zone lymphoma with IgG4-positive cells (IgG4+ MZL; n = 11), and marginal zone lymphoma without IgG4-positive cells (IgG4- MZL; n = 12) of ocular adnexa using immunohistochemical staining. Immunohistochemistry revealed significantly higher AID-intensity index in IgG4-ROD and IgG4+ MZL than IgG4- MZL (p < 0.001 and = 0.001, respectively). The present results suggest that IgG4-RD has several specific causes of AID up-regulation in addition to inflammation, and AID may be a driver of oncogenesis in IgG4-ROD to IgG4+ MZL.

DOI： 10.3390/ijms22084083

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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

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

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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 2020.6

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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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 2020.6

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

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Papers - Nishimura Midori Filiz