Giant cell tumor (GCT) is a bone-destructive benign neoplasm characterized by distinctive multinucleated osteoclast-like giant cells with osteolytic properties distributed among neoplastic stromal cells. GCT is locally aggressive with progressive invasion of adjacent tissues and occasionally displays malignant characteristics including lung metastasis. GCT is characterized genetically by highly recurrent somatic mutations at the G34 position of the H3F3A gene, encoding the histone variant H3.3, in stromal cells. This leads to deregulated gene expression and increased proliferation of mutation-bearing cells. However, when GCT complicates Paget disease of bone (GCT/PDB) it behaves differently, showing a more malignant phenotype with 5-year survival less than 50%. GCT/PDB is caused by a germline mutation in the ZNF687 gene, which encodes a transcription factor involved in the repression of genes surrounding DNA double-strand breaks to promote repair by homologous recombination. Identification of these driver mutations led to novel diagnostic tools for distinguishing between these two tumors and other osteoclast-rich neoplasms. Herein, we review the clinical, histological, and molecular features of GCT in different contexts focusing also on pharmacological treatments.

巨细胞瘤（GCT）是一种骨破坏性良性肿瘤，其特征在于独特的多核破骨细胞样巨细胞，其溶骨特性分布在赘生性基质细胞之间。GCT具有局部侵袭性，邻近组织逐渐浸润，偶尔显示出恶性特征，包括肺转移。GCT的遗传学特征是基质细胞中H3F3A基因G34位置的高重复性体细胞突变，该基因编码组蛋白变体H3.3。这导致基因表达失调和携带突变的细胞的增殖增加。但是，当GCT使Paget骨疾病（GCT / PDB）复杂化时，其表现将有所不同，表现出更加恶性的表型，其5年生存率低于50％。GCT / PDB是由ZNF687基因编码的转录因子参与抑制DNA双链断裂周围的基因，从而通过同源重组促进修复。这些驱动程序突变的鉴定导致了用于区分这两种肿瘤和其他富含破骨细胞的肿瘤的新型诊断工具。在本文中，我们回顾了GCT在不同情况下的临床，组织学和分子特征，重点也放在药理学治疗上。