骨来源肿瘤的分子病理学进展

Recent progress of molecular pathology for bone tumors

形态学以及经典的免疫组化仍是骨来源肿瘤诊断的基石,但以二代测序为基础的分子病理学的蓬勃发展已改进了目前的诊断技术。同时,分子病理学也进一步为骨来源肿瘤的治疗策略提供线索,用于预测肿瘤的生物学行为。基于分子异常的新病种的文献报道不断涌现,让肿瘤的分类从形态学向分子生物学转换。目前,骨肿瘤可以简单分为简单核型和复杂核型两类,前者包括了特殊异位、基因点突变、特殊基因扩增等,而后者往往缺乏特定的变异。本文基于2019年世界卫生组织(World Health Organization,WHO)(第5版)新的骨肿瘤分类,对骨肿瘤的分子病理学更新进行归类和总结。新的基因型的发现有助于骨肿瘤的诊断与鉴别诊断,甚至可以为后续的内科治疗提供新的思路。其中以巨细胞来源的骨的肿瘤的H3F3A p.G34W、软骨母细胞瘤的H3F3B p.K36M、软骨肉瘤的IDH1/2突变、动脉瘤样骨囊肿的USP6重排等成为近年来骨肿瘤分子病理学革新的标志。

Although classic morphology is the cornerstone for the diagnosis of bone tumors,the rapidly developed molecular pathology based on Next Generation Sequencing(NGS)has evolved current diagnostic techniques.At the same time,new disease entities based on molecular abnormalities were constantly reported,which converted the morphological pathological classifications into molecular categories.At present,bone tumors could be roughly classified as tumors with simple karyotypes and those with complex karyotypes by molecular alterations.The previous classification can be subclassified as tumors that carry specific translocations,somatic gene mutations,or those with specific amplifications.However,the later groups usually lack specific alterations.The present review discusses various updates on molecular pathology in detail based on new categories of bone tumors proposed by World Health Organization(WHO)in 2019 aiming to further provide guidance for evidenced-based treatment.Some examples are included,such as giant cell tumor of bone(H3F3A p.G34W),chondroblastoma(H3F3B p.K36M),chondrosarcoma(IDH1/2 mutation),aneurysmal bone cyst(USP6 rearrangements)and so on.All mutual alterations play an increasingly important role in reaching a diagnosis and in patients management.