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• A Comprehensive Study of the Immunophenotype and its Clinicopathological Significance in Adult T-cell Leukemia/Lymphoma

  Tomoko Tamaki, Kennosuke Karube, Shugo Sakihama, Yuma Tsuruta, Ryoko Awazawa, Masaki Hayashi, Norihiro Nakada, Hirofumi Matsumoto, Nobutake Yagi, Kazuiku Ohshiro, Iwao Nakazato, Sakiko Kitamura, Yukiko Nishi, Takuya Miyagi, Sayaka Yamaguchi, Sawako Nakachi, Satoko Morishima, Hiroaki Masuzaki, Kenzo Takahashi, Takuya Fukushima, Naoki Wada

  Modern Pathology ( Modern Pathology )  36 ( 8 ) 100169 - 100169   2023.08 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell tumor caused by human T-lymphotropic virus type 1 (HTLV-1). The typical ATLL immunophenotypes are described in the 2017 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (positive: CD2, CD3, CD5, CD4, and CD25; negative: CD7, CD8, and cytotoxic markers; and partially positive: CD30, CCR4, and FOXP3). However, limited studies are available on the expression of these markers, and their mutual relationship remains unknown. Furthermore, the expression status of novel markers associated with T-cell lymphomas, including Th1 markers (T-bet and CXCR3), Th2 markers (GATA3 and CCR4), T follicular helper markers (BCL6, PD1, and ICOS), and T-cell receptor (TCR) markers, and their clinicopathologic significance is unclear. In this study, we performed >20 immunohistochemical stains in 117 ATLL cases to determine the comprehensive immunophenotypic profile of ATLL, which were compared on the basis of clinicopathologic factors, including morphologic variants (pleomorphic vs anaplastic), biopsy locations, treatments, Shimoyama classification-based clinical subtype, and overall survival. CD3+/CD4+/CD25+/CCR4+ was considered a typical immunophenotype of ATLL, but approximately 20% of cases did not conform to this pattern. Simultaneously, the following new findings were obtained: (1) most cases were negative for TCR-β and TCR-δ (104 cases, 88.9%), indicating the usefulness of negative conversion of TCR expression to provide differentiation from other T-cell tumors; (2) the positivity of CD30 and CD15 and the negativity of FOXP3 and CD3 were significantly associated with anaplastic morphology; and (3) atypical cases, such as T follicular helper marker-positive (12 cases, 10.3%) and cytotoxic molecule-positive cases (3 cases, 2.6%), were identified. No single markers could predict the overall survival among patients with acute/lymphoma subtypes of ATLL. The results of this study illustrate the diversity of ATLL phenotypes. In T-cell tumors occurring in HTLV-1 carriers, the possibility of ATLL should not be eliminated even when the tumor exhibits an atypical phenotype, and the confirmation of HTLV-1 in the tissue is recommended.

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• Gene expression profile of adult T-cell leukemia/lymphoma with human T-cell lymphotropic virus type 1-infected Hodgkin and Reed-Sternberg-like cells is more similar to classic Hodgkin lymphoma than typical adult T-cell leukemia/lymphoma.

  Miyagi S, Mori K, Miyawaki K, Shimo M, Tamaki T, Sakihama S, Takatori M, Akashi K, Karube K, Kato K

  Haematologica     2026.04 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• Integrated genetic analyses identified T-cell neoplasms other than adult T-cell leukemia/lymphoma in HTLV-1 carriers

  Yu Naito, Takahiko Yasuda, Shugo Sakihama, Masayuki Aiba, Kazuho Morichika, Kana Miyazaki, Hiroshi Imai, Ayako Masaki , Takuji Tsuyuki, Satoko Shimada, Makoto Yoshimitsu, Hajime Aoyama, Norihiro Nakada, Takashi Miyagi, Tomoko Tamaki, Bo-Jung Chen, Chang-Tsu Yuan, Takuya Fukushima, Shih-Sung Chuang, Kennosuke Karube

  Blood Advances ( Blood Advances )  10 ( 5 ) 1670 - 1674   2026.03 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• Anaplastic thyroid carcinoma with squamous differentiation and diverse cytology

  SHIMABUKURO Takako, HIGUCHI Kayoko, TATETSU Chie, WADA Naoki, TAMAKI Tomoko

  The Journal of the Japanese Society of Clinical Cytology ( The Japanese Society of Clinical Cytology )  64 ( 2 ) 94 - 101   2025.03 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  <p><i><b>Background</b></i> : Anaplastic thyroid carcinoma is a rare, but highly malignant disease. Herein, we report a case of anaplastic thyroid carcinoma that showed a variety of cytological findings on fine-needle aspiration cytology.</p><p><i><b>Case</b></i> : A female patient in her 60s presented to our hospital with a rapidly enlarging neck mass. Cervical computed tomography and cervical ultrasonography revealed a mass in the right lobe of the thyroid gland and an enlarged right cervical lymph node, both of which were suspected as being malignant. Fine-needle aspiration cytology (FNAC) of the mass in the thyroid gland revealed keratinized atypical cells, which led to the suspicion of squamous cell carcinoma. Postoperative histopathological examination of the excised thyroid gland exhibited features of both papillary and anaplastic thyroid carcinomas, and the final diagnosis was anaplastic thyroid carcinoma with squamous differentiation. A review of the cytology findings revealed papillary carcinoma components, diverse multinucleated giant cells, and neutrophilic infiltration within highly atypical cell clusters.</p><p><i><b>Conclusion</b></i> : When keratinizing atypical cells are found on FNAC, conditions that should be considered in the differential diagnosis include anaplastic carcinoma with squamous differentiation, squamous metaplasia of papillary carcinoma, intrathyroidal thymic carcinoma, sclerosing mucoepidermoid carcinoma with eosinophilia, and diffuse sclerosing papillary carcinoma. Anaplastic carcinoma with squamous differentiation is presumed when necrotic and inflammatory cells are seen in the background, and large atypical cells with various morphologies and mitoses are seen.</p>

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

  Karube, K; Sakihama, S; Takatori, M; Morichika, K; Tamaki, T; Wada, N; Fukushima, T

  LEUKEMIA RESEARCH ( 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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Other Papers 【 display / non-display 】

Other Papers 【 display / non-display 】

• 免疫チェックポイント阻害薬を放射線化学療法に追加して加療した上部尿路上皮癌の治療経験(Clinical experience of Pembrolizumab for renal pelvic and ureteral cancer after chemo-radiation therapy)

  足立 秀幸, 田中 一輝, 佐々木 翔平, 川越 淳平, 島袋 浩勝, 向山 秀樹, 橋本 成司, 真鍋 良彦, 平安名 常一, 玉城 智子

  日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 )  110回   PP32 - 06   2023.04

   

• 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

   

Academic Awards 【 display / non-display 】

Academic Awards 【 display / non-display 】

• Young Investigator Award

  2024.11    

• Young Researcher Academic Encouragement Award, Regional Contribution Category

  2023.06    

• Special Research Promotion Project, Ryukyu Medical Association Award

  2023.03   Ryukyu Medical Association  

  Winner: Tomoko Tamaki

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

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

• Grant-in-Aid for Young Scientists(S)

  Project Year: 2025.04  -  2027.03 

  Direct: 2,900,000 (YEN)  Overheads: 870,000 (YEN)  Total: 3,770,000 (YEN)