Karube Kennosuke, Sakihama Shugo, Takatori Mitsuyoshi, Morichika Kazuho, Tamaki Tomoko, Wada Naoki, Fukushima Takuya
Department of Pathology and Laboratory Medicine, Graduate School of Medicine, Nagoya University, Nagoya, Japan; Laboratory of Hemato-Immunology, Graduate School of Health Sciences, University of the Ryukyus, Nishihara, Japan.
Laboratory of Hemato-Immunology, Graduate School of Health Sciences, University of the Ryukyus, Nishihara, Japan.
Leuk Res. 2025 Jan;148:107634. doi: 10.1016/j.leukres.2024.107634. Epub 2024 Dec 6.
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.
成人T细胞白血病/淋巴瘤（ATLL）是一种由1型人类T细胞白血病病毒（HTLV-1）感染引起的外周T细胞淋巴瘤。尽管世界卫生组织第5版分类（WHO-5）在ATLL的疾病概念方面与世界卫生组织第4版修订分类（WHO-4R）相比没有重大变化，但WHO-5新引入了基本和理想的诊断标准，即分别为“具有成熟T细胞表型的肿瘤性淋巴细胞增殖；经证实的HTLV-1携带者”和“HTLV-1单克隆整合的鉴定”。为满足理想标准，除了传统使用的Southern印迹杂交外，还引入了一种结合HBZ原位杂交（HBZ-ISH）和tax聚合酶链反应（tax-PCR）的新诊断方法来鉴定HTLV-1，特别是在仅可获得福尔马林固定石蜡包埋（FFPE）标本的情况下。形态学上，多形性和间变性大细胞型占大多数病例，而小变异型，如伴有皮肤病变反应的ATLL、血管免疫母细胞性T细胞淋巴瘤样变异型和经典霍奇金淋巴瘤样变异型，也应作为诊断陷阱加以注意。表型上，约80%的ATLL病例表现出CD3+CD4+CD25+CCR4+的典型表型，而约10%表现出非典型表型，如T滤泡辅助细胞样表型。观察到许多主要与T细胞受体信号通路相关的基因异常，除信号转导和转录激活因子3（STAT3）外，大多数在侵袭性类型中比在惰性类型中更常见，这表明ATLL的致病过程具有异质性。在本综述中，我们介绍了淋巴瘤新分类时代ATLL分子发病机制和组织病理学发现的最新研究结果，为未来的研究和分类提供依据。
