Genetic Basis of Extramedullary Plasmablastic Transformation of Multiple Myeloma
Genetic Basis of Extramedullary Plasmablastic Transformation of Multiple Myeloma
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DOI：
10.1097/pas.0000000000001459
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发表时间：
2020-06-01
影响因子：
5.6
通讯作者：
Xiao, Wenbin
中科院分区：
文献类型：
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作者：
Liu, Ying;Jelloul, Fatima;Xiao, Wenbin
在多发性骨髓瘤患者中，骨髓中的血浆白蛋白转化是罕见的，并且与不良结局相关。在骨髓中存在小的成熟克隆浆细胞的患者中，不一致的髓外浆细胞转化的意义尚未得到很好的研究。在这里，我们报告了10名此类患者（男性/女性：6/4，中位年龄：65岁，范围：48至76岁）的临床病理、细胞遗传学和分子特征，确诊为骨髓中由小而成熟的浆细胞组成的多发性骨髓瘤，同时或随后发生髓外浆母细胞转化。8例有可用生存数据的患者显示，尽管进行了积极治疗，甚至在低水平骨髓受累的患者中，诊断为髓外浆细胞转化后的中位生存期为4.5个月，总体表现为积极的临床病程。病理学上，髓外浆细胞性骨髓瘤与相应的骨髓浆细胞克隆相关，通过免疫组织化学显示高水平的CMYC和/或P53表达，高Ki-67增殖指数，并且与骨髓对应物相比，具有更复杂的基因组畸变，包括RAS通路中的频繁突变和MYC重排。总之，尽管由于本研究的回顾性性质，未对所有病例进行统一的遗传学和免疫组化研究，但我们的数据表明，多发性骨髓瘤的不一致髓外浆细胞转化具有侵袭性临床病程，其特征为RAS通路中的频繁突变和更复杂的基因组异常。
In patients with multiple myeloma, plasmablastic transformation in the bone marrow is rare and associated with poor outcomes. The significance of discordant extramedullary plasmablastic transformation in patients with small, mature clonal plasma cells in the bone marrow has not been well studied. Here, we report the clinicopathologic, cytogenetic, and molecular features of 10 such patients (male/female: 6/4, median age: 65 y, range: 48 to 76 y) with an established diagnosis of multiple myeloma in the bone marrow composed of small, mature plasma cells in parallel with a concurrent or subsequent extramedullary plasmablastic transformation. Eight patients with available survival data showed an overall aggressive clinical course with a median survival of 4.5 months after the diagnosis of extramedullary plasmablastic transformation, despite aggressive treatment and even in patients with low-level bone marrow involvement. Pathologically, the extramedullary plasmablastic myeloma were clonally related to the corresponding bone marrow plasma cells, showed high levels of CMYC and/or P53 expression with a high Ki-67 proliferation index by immunohistochemistry and harbored more complex genomic aberrations including frequent mutations in the RAS pathway and MYC rearrangements compared with their bone marrow counterparts. In summary, although genetic and immunohistochemical studies were not uniformly performed on all cases due to the retrospective nature of this study, our data suggest that discordant extramedullary plasmablastic transformation of multiple myeloma has an aggressive clinical course and is characterized by frequent mutations in the RAS pathway and more complex genomic abnormalities.