Institute of Pathology and Neuropathology, Comprehensive Cancer Center and University Hospital Tuebingen, Liebermeisterstr. 8, 72076, Tübingen, Germany.
Medical Department, Hematology and Oncology, Comprehensive Cancer Center Tuebingen, University of Tuebingen, Tübingen, Germany.
Virchows Arch. 2019 Dec;475(6):795-798. doi: 10.1007/s00428-019-02608-7. Epub 2019 Jul 17.
The traditional concept of unidirectional maturation of hematopoietic cells has been called into question due to the recognition of lineage plasticity, which is increasingly found also in the clonal evolution of hematopoietic and lymphoid malignancies. Here we present an unusual case of a patient with TP53-mutated chronic lymphocytic leukemia (CLL) treated with a PI3Kδ inhibitor evolving to clonally related Langerhans cell histiocytosis (LCH) with acquired BRAF V600E and STK11 mutations and loss of expression of PAX-5 and other examined B cell markers. In indolent B cell lymphoma, transformation to a more aggressive high-grade lymphoma occurs frequently during the course of disease and is thought to be caused by clonal evolution. Our case further supports the concept of significant lineage plasticity in lymphomas and raises the question of a potential role of novel pharmacologic agents in clonal evolution.
由于认识到谱系可塑性，造血细胞的传统单向成熟概念受到质疑，而谱系可塑性在造血和淋巴恶性肿瘤的克隆进化中也越来越常见。在这里，我们介绍了一例不寻常的患者，该患者患有 TP53 突变的慢性淋巴细胞白血病 (CLL)，经 PI3Kδ 抑制剂治疗后，出现与克隆相关的朗格汉斯细胞组织细胞增生症 (LCH)，并获得 BRAF V600E 和 STK11 突变以及 PAX-5 和其他检查的 B 细胞标志物表达缺失。在惰性 B 细胞淋巴瘤中，在疾病过程中经常会转化为更具侵袭性的高级别淋巴瘤，据认为这是由克隆进化引起的。我们的病例进一步支持了淋巴瘤中明显的谱系可塑性概念，并提出了新型药物在克隆进化中潜在作用的问题。
