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Published Papers 【 display / non-display 】

• Extranodal natural killer/T-cell lymphoma with lung involvement in a young adult with suspected mosquito bite hypersensitivity: A case report.

  Mariko Higa, Eriko Atsumi, Hironobu Hoshino, Mahito Yamashiro, Tomo Nakajima, Mariko Tomita, Hiroaki Masuzaki, Naoki Wada, Isoko Owan

  Respiratory investigation   63 ( 5 ) 872 - 876   2025.09 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  A young adult with suspected pulmonary lymphoma was diagnosed with extranodal natural killer/T-cell lymphoma (ENKTL). The patient had a history of possible mosquito bite hypersensitivity (MBH), suggesting a potential association between MBH and ENKTL. Although ENKTL typically affects middle-aged adults, it has rarely been reported in children with MBH or chronic active Epstein-Barr virus (EBV) disease. This case highlights the challenges of obtaining pathological confirmation from small biopsy samples of pulmonary ENKTL. Detailed history taking and EBV DNA testing may aid in diagnosis, particularly in younger patients.

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• Spontaneous Regression of Cranial Vault Lymphoma: A Case Report.

  Kazutaka Kishaba, Yohei Hokama, Tomomi Kuninaka, Hirofumi Miyahira, Mariko Tomita, Naoki Wada, Akira Yogi, Tadashi Hamasaki

  Cureus   17 ( 7 ) e87472   2025.07 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Primary lymphoma of the cranial vault is extremely rare and often mimics other cranial bone tumors on imaging. We report a 75-year-old female with a scalp mass and occasional headache. MRI revealed a lesion centered in the cranial vault, extending both intra- and extracranially. The initial diagnosis was intraosseous meningioma, but the lesion rapidly decreased in size over a few weeks without any treatment. Biopsy revealed histology consistent with non-Hodgkin lymphoma. Further classification suggested marginal zone B-cell lymphoma, a rare entity arising in the cranial vault. We managed the patient with imaging follow-up and found no recurrence for six months. The present case supports the notion that indolent lymphomas arising in the cranial bone share regression potential seen in other tissues. Accurate diagnosis requires histopathological confirmation even when lesions regress spontaneously. A watch-and-wait approach may be reasonable for selected cases, with careful monitoring for progression or transformation.

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• Recent progress in pathological understanding of adult T-cell leukemia/lymphoma in the new classification era.

  Kennosuke Karube, Shugo Sakihama, Mitsuyoshi Takatori, Kazuho Morichika, Tomoko Tamaki, Naoki Wada, Takuya Fukushima

  Leukemia research   148   107634 - 107634   2025.01 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma caused by Human T-cell leukemia virus type 1 (HTLV-1) infection. Although the 5th Edition of the WHO classification (WHO-5) did not make drastic changes regarding the disease concept of ATLL from the revised 4th Edition of the WHO classification (WHO-4R), WHO-5 newly introduced the essential and desirable diagnostic criteria, namely, "neoplastic lymphoid cell proliferation with mature T-cell phenotype; proven HTLV-1 carriership" and "identification of monoclonal integration of HTLV-1", respectively. To satisfy the desirable criteria, a new diagnostic method using a combination of HBZ-ISH and tax-PCR was introduced for the identification of the HTLV-1 in addition to the conventionally used Southern blot hybridization, especially in the case when only FFPE specimens are available. Morphologically, pleomorphic- and anaplastic large cell-type, account for most cases, while minor variants, ATLL with dermatopathic reaction, angioimmunoblastic T-cell lymphoma-like variant, and classic Hodgkin lymphoma-like variant, should also be noted as diagnostic pitfalls. Phenotypically, about 80 % of ATLL cases show a typical phenotype of CD3 + CD4 +CD25 +CCR4 + , while about 10 % show atypical phenotypes such as T follicular helper cell-like one. Many genetic abnormalities, mainly associated with the TCR signaling pathway, are observed, and most are more frequent in the aggressive type than in the indolent type, except for STAT3, indicating the heterogeneous pathogenic process of ATLL. In this review, we present the latest findings on molecular pathogenesis and histopathological findings of ATLL in the era of the new classification of lymphomas, serving as a basis for future research and classification.

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• Standardization of CD30 immunohistochemistry staining among three automated immunostaining platforms.

  Masafumi Seki, Akira Satou, Renji Funato, Tomoko Tamaki, Naoki Wada, Norihiro Nakada, Hirofumi Matsumoto, Iwao Nakazato, Eriko Wada, Kaneko Sakurai, Toyonori Tsuzuki, Kennosuke Karube

  Pathology international   74 ( 9 ) 530 - 537   2024.09 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  The identification of CD30 expression by immunohistochemistry is essential for the treatment of lymphomas using an antibody-drug conjugate targeting CD30. However, no standardized protocol for CD30 staining has been available. In this study, we compared three common automated immunostaining platforms {Bond III (B III), Dako Omnis (DO) and Ventana BenchMark ULTRA (VBMU)}. A primary antibody for CD30, the Ber-H2 clone, was diluted 50- to 400-fold for B III and DO, and ready-to-use antibody was used for VBMU. An enhancement step using a linker was introduced in all protocols. First, several candidate dilutions were selected for each platform by staining six cases. These candidate conditions were then confirmed with 60 cases of various types of peripheral T-cell lymphomas (PTCLs). The concordance rates of CD30 expression among platforms differed depending on cutoff values and antibody dilutions, except for anaplastic large cell lymphoma. The concordance rates among three platforms in the evaluation of "positive" or "negative" were 100% and 97% when the cutoff values were 1% and 10% respectively, if using 400-diluted antibody in B III and 100-diluted antibody in DO. This study demonstrated the feasibility of equalizing CD30 staining of PTCLs among different platforms by adjusting protocols.

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• A Case of SMARCB1-Deficient Sinonasal Carcinoma With Clear Cell Morphology.

  Tomoko Tamaki, Kyonosuke Teruya, Hitoshi Hirakawa, Mariko Tomita, Naoki Wada

  Cureus   16 ( 5 ) e59684   2024.05 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  SMARCB1 is a gene known to cause carcinogenesis in many soft tissue tumors, including malignant rhabdoid tumors and epithelioid sarcoma. Since the first report of a subtype of sinonasal carcinoma characterized by a deficiency of the SMARCB1 gene in 2014 to date, fewer than 200 cases have been reported. We report a case of SMARCB1-deficient sinonasal carcinoma with clear cell morphology. In our case, there are no evident basaloid or plasmacytoid/rhabdoid tumor cells, which are typical histopathological features of SMARCB1-deficient sinonasal carcinoma. SMARCB1-deficient sinonasal carcinoma is prone to recurrence and has a very poor prognosis. As the development of molecularly targeted agents progresses, therapeutic efficacy is expected to improve. Simultaneously, the importance of early and accurate diagnosis of SMARCB1-deficient sinonasal carcinoma will increase. With the limited information provided by biopsy specimens, it is necessary to confirm the loss of SMARCB1 expression by immunohistochemistry and investigate the presence of SMARCB1 gene deletion by molecular genetics, considering the possibility of SMARCB1-deficient sinonasal carcinoma even in atypical cases without basaloid or plasmacytoid/rhabdoid cell morphology, as in our case.

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Other Papers 【 display / non-display 】

Other Papers 【 display / non-display 】

• 成人T細胞白血病・リンパ腫(ATLL)の病理組織学的形態および免疫表現型に関する検討(A study on histopathological morphology and immunophenotype of adult T-cell leukemia/lymphoma (ATLL))

  玉城 智子, 加留部 謙之輔, 仲田 典宏, 松本 裕文, 仲里 巌, 和田 直樹

  日本病理学会会誌 ( (一社)日本病理学会 )  112 ( 1 ) 274 - 274   2023.03

   

• Standardization of CD30 immunohistochemical staining on different staining platforms

  関雅文, 佐藤啓, 舩戸連嗣, 玉城智子, 和田直樹, 加留部謙之輔

  日本病理学会会誌   112 ( 1 )   2023

   

  J-GLOBAL

• SDPRは子宮体部類内膜癌においてILKを介してALDH1を制御する

  田原 紳一郎, 野島 聡, 大島 健司, 堀 由美子, 倉重 真沙子, 和田 直樹, 本山 雄一, 奥崎 大介, 池田 純一郎, 森井 英一

  日本癌学会総会記事 ( (一社)日本癌学会 )  79回   YSA - 2   2020.10

   

• 肝reactive lymphoid hyperplasiaの1例(A case of reactive lymphoid hyperplasia of the liver)

  野浦 郁恵, 佐々木 香織, 皆見 勇人, 小林 郁江, 大畑 麻衣, 和田 直樹, 田中 さやか, 桑江 優子, 大澤 政彦

  日本病理学会会誌 ( (一社)日本病理学会 )  109 ( 1 ) 350 - 350   2020.03

   

• 動脈炎におけるステロイド治療が及ぼす組織学的変化(Histological change of Arteritis under steroid treatment)

  田中 さやか, 佐々木 香織, 皆見 勇人, 野浦 郁恵, 小林 郁江, 大畑 麻衣, 和田 直樹, 桑江 優子, 大澤 政彦

  日本病理学会会誌 ( (一社)日本病理学会 )  109 ( 1 ) 459 - 459   2020.03

   

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Presentations 【 display / non-display 】

Presentations 【 display / non-display 】

• A study on histopathological morphology and immunophenotype of adult T-cell leukemia/lymphoma (ATLL)

  Tomoko Tamaki, Kennosuke Karube, Norihiro Nakada, Hirofumi Matsumoto, Iwao Nakazato, Naoki Wada

  2023.04  -  2023.04 

• Cytologic Characteristics and Differential Diagnosis of Secretory Carcinoma: An Analysis of 16 Cases

  Kayoko Higuchi, Akihiko Kawahara, Katsuyuki Tsuha, Yuri Kato, Tomoya Minami, Yuko Chibana, Hirofumi Koyama, Naoki Wada, Makoto Urano, Toshitaka Nagao

  第20回日韓細胞診合同会議  (韓国Gunsan city（群山）のGunsan Saemangeum Convention Center(GSCO))  1900.01  -  1900.01 

Grant-in-Aid for Scientific Research 【 display / non-display 】

Grant-in-Aid for Scientific Research 【 display / non-display 】

• Grant-in-Aid for Scientific Research(C)

  Project Year: 2018.04  -  2021.03 

  Direct: 3,500,000 (YEN)  Overheads: 1,050,000 (YEN)  Total: 4,550,000 (YEN)

• Elucidation of the factor involved in the dynamic differentiation of lymphoplasmacytic lymphoma

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2018.04  -  2021.03 

  Investigator(s): WADA Naoki 

  Direct: 3,500,000 (YEN)  Overheads: 4,550,000 (YEN)  Total: 1,050,000 (YEN)

  　View Summary

  Glutamine (Gln) is important not only for cell proliferation but also for differentiation. Although Gln is essential for plasmacytic differentiation of lymphocytes, no study has been done on the effect of Gln on differentiation of tumor cells, such as lymphoma. Here I examined the effect of Gln on plasmacytic differentiation of lymphoplasmacytic lymphoma (LPL) with its cell line. Gln promoted plasmacytic differentiation of LPL, and p38 MAPK signaling pathway mediated such differentiation. I previously reported that the subpopulation with plasmacytic differentiation was vulnerable to apoptosis in LPL. Although it is difficult to lead these findings to the radical therapy, they might help the treatment of LPL.

• The positive marker identification of tumor-initiating cells and the dynamic analyses of them in lymphoplasmacytic lymphoma (LPL)

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2015.04  -  2018.03 

  Investigator(s): WADA Naoki 

  Direct: 3,800,000 (YEN)  Overheads: 1,140,000 (YEN)  Total: 4,940,000 (YEN)

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  MWCL-1 was established as LPL cell line. MWCL-1 cells were classified into three subpopulations by flow cytometric analyses using anti-CD20 and anti-CD138 antibodies: CD20-CD138-, CD20+CD138-, and CD20+CD138+ cells. We searched for markers preferentially expressed in CD20-CD138- cells of MWCL-1 (the candidates for tumor-initiating cells of LPL), and the chemokine receptor CXCR7 was isolated. We also searched for favorable microenvironments for their proliferation, and we found that hypoxia and CXCL12-CXCR7 signaling appeared to be favorable microenvironments. We then examined the effect of plasma-activated medium (PAM) on LPL cell line, and we found that PAM induced plasma cell (CD138 positive) differentiation, which appeared to be mediated by PRDM1α (the transcription factor promoting plasma cell differentiation).

• The positive marker identification of tumor-initiating cells and the dynamic analyses of them in lymphoplasmacytic lymphoma (LPL)

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2015.04  -  2018.03 

  Investigator(s): WADA Naoki 

  Direct: 3,800,000 (YEN)  Overheads: 4,940,000 (YEN)  Total: 1,140,000 (YEN)

  　View Summary

  MWCL-1 was established as LPL cell line. MWCL-1 cells were classified into three subpopulations by flow cytometric analyses using anti-CD20 and anti-CD138 antibodies: CD20-CD138-, CD20+CD138-, and CD20+CD138+ cells. We searched for markers preferentially expressed in CD20-CD138- cells of MWCL-1 (the candidates for tumor-initiating cells of LPL), and the chemokine receptor CXCR7 was isolated. We also searched for favorable microenvironments for their proliferation, and we found that hypoxia and CXCL12-CXCR7 signaling appeared to be favorable microenvironments. We then examined the effect of plasma-activated medium (PAM) on LPL cell line, and we found that PAM induced plasma cell (CD138 positive) differentiation, which appeared to be mediated by PRDM1α (the transcription factor promoting plasma cell differentiation).

• Dynamic analyses of tumor-initiating cells in lymphoplasmacytic lymphoma (LPL)

  Grant-in-Aid for Young Scientists(B)

  Project Year: 2013.04  -  2015.03 

  Investigator(s): WADA NAOKI 

  Direct: 3,200,000 (YEN)  Overheads: 960,000 (YEN)  Total: 4,160,000 (YEN)

  　View Summary

  MWCL-1 was established as LPL cell line. MWCL-1 cells were classified into three subpopulations using a flow cytometer with anti-CD20 and anti-CD138 antibodies: CD20-CD138-, CD20+CD138-, and CD20+CD138+. When cultured, CD20-CD138- cells yielded all three subpopulations. Compared to the other subpopulations, CD20-CD138- cells possessed the efficient ROS expelling and in vitro colony formation activities, and were resistant to apoptosis. These results suggested that CD20-CD138- cells might be a candidate for tumor-initiating cells in LPL. Low oxygen culture of MWCL-1 induced the production of CD20-CD138- cells, and this result suggested that hypoxia was an advantageous microenvironment for CD20-CD138- cells. CXCR7 mRNA/protein expression was the highest in CD20-CD138- cells. When CXCL12, a ligand of CXCR7, was added, the proportion of CD20-CD138- cells significantly increased. CXCL12-CXCR7 signaling might exert a great influence on CD20-CD138- cells.

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Social Activity 【 display / non-display 】

• 2024.01