PDF(Pubmed)
Abstract：
Tenosynovial giant cell tumors (TGCTs) are rare, locally aggressive, mesenchymal neoplasms, most often arising from the synovium of joints, bursae, or tendon sheaths. Surgical resection is the first-line treatment, but recurrence is common, with resulting impairments in patients\' mobility and quality of life. Developing and optimizing the role of systemic pharmacologic therapies in TGCT management requires an understanding of the underlying disease mechanisms. The colony-stimulating factor 1 receptor (CSF1R) has emerged as having an important role in the neoplastic processes underlying TGCT. Lesions appear to contain CSF1-expressing neoplastic cells derived from the synovial lining surrounded by non-neoplastic macrophages that express the CSF1R, with lesion growth stimulated by both autocrine effects causing proliferation of the neoplastic cells themselves and by paracrine effects resulting in recruitment of CSF1 R-bearing macrophages. Other signaling pathways with evidence for involvement in TGCT pathogenesis include programmed death ligand-1, matrix metalloproteinases, and the Casitas B-cell lymphoma family of ubiquitin ligases. While growing understanding of the pathways leading to TGCT has resulted in the development of both regulatory approved and investigational therapies, more detail on underlying disease mechanisms still needs to be elucidated in order to improve the choice of individualized therapies and to enhance treatment outcomes.
摘要：
腱鞘膜巨细胞瘤（TGCT）是罕见的，当地的侵略性，间充质肿瘤,最常见的是关节滑膜，法氏囊,或腱鞘。手术切除是一线治疗,但是复发是很常见的，导致患者活动能力和生活质量受损。开发和优化全身药物疗法在TGCT管理中的作用需要了解潜在的疾病机制。集落刺激因子1受体（CSF1R）在TGCT的肿瘤形成过程中起着重要作用。病变似乎含有来自滑膜衬里的表达CSF1的肿瘤细胞，这些细胞被表达CSF1R的非肿瘤巨噬细胞包围，由引起肿瘤细胞自身增殖的自分泌效应和导致携带CSF1R的巨噬细胞募集的旁分泌效应刺激的病变生长。其他有证据表明参与TGCT发病机制的信号通路包括程序性死亡配体-1，基质金属蛋白酶，和CasitasB细胞淋巴瘤泛素连接酶家族。虽然对导致TGCT的途径的日益理解导致了监管批准和研究疗法的发展，关于潜在疾病机制的更多细节仍需阐明,以改善个体化治疗的选择并提高治疗效果.
