A Comprehensive Study of the Immunophenotype and its Clinicopathologic 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

doi:10.1016/j.modpat.2023.100169

A Comprehensive Study of the Immunophenotype and its Clinicopathologic Significance in Adult T-Cell Leukemia/Lymphoma

Mod Pathol. 2023 Aug;36(8):100169. doi: 10.1016/j.modpat.2023.100169. Epub 2023 Mar 29.

Authors

Tomoko Tamaki¹, Kennosuke Karube², Shugo Sakihama³, Yuma Tsuruta⁴, Ryoko Awazawa⁵, Masaki Hayashi⁶, Norihiro Nakada⁴, Hirofumi Matsumoto⁴, Nobutake Yagi⁷, Kazuiku Ohshiro⁸, Iwao Nakazato⁹, Sakiko Kitamura¹⁰, Yukiko Nishi¹⁰, Takuya Miyagi¹¹, Sayaka Yamaguchi¹¹, Sawako Nakachi¹⁰, Satoko Morishima¹⁰, Hiroaki Masuzaki¹⁰, Kenzo Takahashi¹¹, Takuya Fukushima³, Naoki Wada¹²

Affiliations

¹ Department of Pathology and Oncology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan. Electronic address: tamakit@med.u-ryukyu.ac.jp.
² Department of Pathology and Laboratory Medicine, Graduate School of Medicine, Nagoya University, Aichi, Japan; Laboratory of Hemato-Immunology, Graduate School of Health Sciences, University of the Ryukyus, Nishihara, Japan. Electronic address: karube@med.nagoya-u.ac.jp.
³ Laboratory of Hemato-Immunology, Graduate School of Health Sciences, University of the Ryukyus, Nishihara, Japan.
⁴ Department of Pathology, Nakagami Hospital, Okinawa, Japan.
⁵ Department of Dermatology, Nakagami Hospital, Okinawa, Japan.
⁶ Department of Hematology, Nakagami Hospital, Okinawa, Japan.
⁷ Department of Dermatology, Okinawa Prefectural Nanbu Medical Center and Children's Medical Center, Okinawa, Japan.
⁸ Department of Hematology and Oncology, Okinawa Prefectural Nanbu Medical Center and Children's Medical Center, Okinawa, Japan.
⁹ Department of Pathology, Okinawa Prefectural Nanbu Medical Center and Children's Medical Center, Okinawa, Japan.
¹⁰ Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
¹¹ Department of Dermatology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
¹² Department of Pathology and Oncology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

PMID: 36997002
DOI: 10.1016/j.modpat.2023.100169

Abstract

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.

Keywords: adult T-cell leukemia/lymphoma; immunohistochemistry; morphology; phenotype.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Forkhead Transcription Factors
Human T-lymphotropic virus 1* / genetics
Humans
Leukemia-Lymphoma, Adult T-Cell*
Lymphoma*
Lymphoma, T-Cell*

Substances

Forkhead Transcription Factors