ALK-Negative Anaplastic Large Cell Lymphoma: Current Concepts and Molecular Pathogenesis of a Heterogeneous Group of Large T-Cell Lymphomas.
ALK-Negative Anaplastic Large Cell Lymphoma: Current Concepts and Molecular Pathogenesis of a Heterogeneous Group of Large T-Cell Lymphomas.
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ALK 阴性间变性大细胞淋巴瘤：异质性大 T 细胞淋巴瘤的当前概念和分子发病机制。
DOI：
10.3390/cancers13184667
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发表时间：
2021-09-17
期刊：
影响因子：
5.2
通讯作者：
Zarate-Osorno A
中科院分区：
文献类型：
--
作者：
Pina-Oviedo S;Ortiz-Hidalgo C;Carballo-Zarate AA;Zarate-Osorno A
ALK-间变性大细胞淋巴瘤（ALK-ALCL）是CD 30+大T细胞淋巴瘤的一种罕见亚型，通常累及老年人，预后不良。识别其组织病理学谱、亚型和其他类似ALK-ALCL的肿瘤对于避免做出可能导致患者治疗不当的错误诊断至关重要。近年来，一些重要的研究已经确定了经常性的分子改变，揭示了这种淋巴瘤的发病机制。然而，另一方面，将所有这些庞大的信息整合成一个简洁的形式变得具有挑战性。在本综述中，我们不仅提供了ALK-ALCL组织病理学结果的更详细的观点，而且还试图提供这种类型淋巴瘤相关遗传和分子改变的更简化的观点，我们认为这是迄今为止不可用的。间变性大细胞淋巴瘤（ALCL）是CD 30+大T细胞淋巴瘤（TCL）的一种亚型，占所有成人非霍奇金淋巴瘤的约2%。根据是否存在间变性淋巴瘤激酶（ALK）的重排和表达，ALCL分为ALK+和ALK-，两者在临床和病理学上均不同。本综述重点关注ALK-ALCL及其亚型（系统性、原发性皮肤（pc-ALCL）和乳房植入体相关（BIA-ALCL））的历史要点、临床特征、组织病理学、鉴别诊断和相关细胞遗传学和分子学改变。最近的研究已经确定了经常性的遗传变异，这TCL。在系统性ALK-ALCL中，分别在30%和8%的病例中检测到DUSP 22和TP 63重排，而其余病例的这些重排均为阴性。在pc-ALCL中观察到这些重排的相似分布，而在BIA-ALCL中未检测到重排。此外，系统性ALK-ALCL（除DUSP 22重排病例外）携带JAK 1和/或STAT 3突变，导致JAK/STAT信号通路激活。在BIA-ALCL中也发现了JAK 1/3和STAT 3突变，但在pc-ALCL中未发现。虽然这些改变的发病机制尚未完全了解，但其中大多数具有预后价值，并为这种TCL亚型的潜在靶向治疗打开了大门。
ALK- anaplastic large cell lymphoma (ALK- ALCL) is a rare subtype of CD30+ large T-cell lymphoma that typically affects older adults and has a poor prognosis. Recognition of its histopathologic spectrum, subtypes, and of other tumors that can resemble ALK- ALCL is crucial to avoid making a wrong diagnosis that could result in inappropriate treatment for a patient. In recent years, several important studies have identified recurrent molecular alterations that have shed light on the pathogenesis of this lymphoma. However, on the other hand, putting all this vast information together into a concise form has become challenging. In this review, we present not only a more detailed view of the histopathologic findings of ALK- ALCL but also, we attempt to provide a more simplified perspective of the relevant genetic and molecular alterations of this type of lymphoma, that in our opinion, is not available to date. Anaplastic large cell lymphoma (ALCL) is a subtype of CD30+ large T-cell lymphoma (TCL) that comprises ~2% of all adult non-Hodgkin lymphomas. Based on the presence/absence of the rearrangement and expression of anaplastic lymphoma kinase (ALK), ALCL is divided into ALK+ and ALK-, and both differ clinically and prognostically. This review focuses on the historical points, clinical features, histopathology, differential diagnosis, and relevant cytogenetic and molecular alterations of ALK- ALCL and its subtypes: systemic, primary cutaneous (pc-ALCL), and breast implant-associated (BIA-ALCL). Recent studies have identified recurrent genetic alterations in this TCL. In systemic ALK- ALCL, rearrangements in DUSP22 and TP63 are detected in 30% and 8% of cases, respectively, while the remaining cases are negative for these rearrangements. A similar distribution of these rearrangements is seen in pc-ALCL, whereas none have been detected in BIA-ALCL. Additionally, systemic ALK- ALCL—apart from DUSP22-rearranged cases—harbors JAK1 and/or STAT3 mutations that result in the activation of the JAK/STAT signaling pathway. The JAK1/3 and STAT3 mutations have also been identified in BIA-ALCL but not in pc-ALCL. Although the pathogenesis of these alterations is not fully understood, most of them have prognostic value and open the door to the use of potential targeted therapies for this subtype of TCL.
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0.1
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通讯作者：
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