Department of Pathology and Oncology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
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.
Mod Pathol. 2023 Aug;36(8):100169. doi: 10.1016/j.modpat.2023.100169. Epub 2023 Mar 29.
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.
成人 T 细胞白血病/淋巴瘤 (ATLL) 是一种由人类 T 淋巴细胞病毒 1 (HTLV-1) 引起的成熟 T 细胞肿瘤。2017 年世界卫生组织造血和淋巴组织肿瘤分类将典型的 ATLL 免疫表型描述为：（阳性：CD2、CD3、CD5、CD4 和 CD25；阴性：CD7、CD8 和细胞毒性标志物；部分阳性：CD30、CCR4 和 FOXP3）。然而，关于这些标志物的表达的研究有限，它们之间的相互关系尚不清楚。此外，与 T 细胞淋巴瘤相关的新型标志物的表达状态，包括 Th1 标志物（T-bet 和 CXCR3）、Th2 标志物（GATA3 和 CCR4）、滤泡辅助 T 细胞标志物（BCL6、PD1 和 ICOS）和 T 细胞受体（TCR）标志物的表达状态及其临床病理意义尚不清楚。在这项研究中，我们对 117 例 ATLL 病例进行了超过 20 种免疫组化染色，以确定 ATLL 的综合免疫表型谱，并根据临床病理因素（包括形态变异型（多形性与间变性）、活检部位、治疗、Shimoyama 临床亚型分类和总生存）进行比较。CD3+/CD4+/CD25+/CCR4+被认为是 ATLL 的典型免疫表型，但约 20%的病例不符合这种模式。同时，还获得了以下新发现：（1）大多数病例 TCR-β 和 TCR-δ 阴性（104 例，88.9%），表明 TCR 表达的阴性转化有助于与其他 T 细胞肿瘤区分；（2）CD30 和 CD15 的阳性以及 FOXP3 和 CD3 的阴性与间变性形态显著相关；（3）鉴定出非典型病例，如滤泡辅助 T 细胞标志物阳性（12 例，10.3%）和细胞毒性分子阳性病例（3 例，2.6%）。急性/淋巴瘤亚型 ATLL 患者中，没有单一的标志物可以预测总生存。本研究结果表明 ATLL 表型的多样性。在 HTLV-1 携带者中发生的 T 细胞肿瘤中，即使肿瘤表现为非典型表型，也不应排除 ATLL 的可能性，建议在组织中确认 HTLV-1。
