Clinical and Pathologic Spectrum of DDX41-Mutated Hematolymphoid Neoplasms
Clinical and Pathologic Spectrum of DDX41-Mutated Hematolymphoid Neoplasms
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DOI：
10.1093/ajcp/aqab027
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发表时间：
2021-04-30
影响因子：
3.5
通讯作者：
Cook, James R.
中科院分区：
文献类型：
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作者：
Goyal, Tanu;Tu, Zheng Jin;Cook, James R.
目的：本研究旨在进一步描述 DDX41 突变的血液淋巴恶性肿瘤的临床病理学谱。方法：我们从一组已知或疑似血液系统疾病中鉴定出 DDX41 突变，并回顾了相应的临床、遗传、表型和形态学发现。结果：在 20 例患者中发现了 DDX41 突变。 1,371例中（1.4%），包括8例急性髓性白血病（AML）、5例骨髓增生异常综合征（MDS）、2例治疗相关MDS/AML、1例原发性骨髓纤维化、1例慢性粒细胞白血病、1例意义不明的克隆性血细胞减少症（CCUS）、1例T细胞大颗粒 淋巴细胞白血病（T-LGL）1例，多发性骨髓瘤1例。 DDX41 突变肿瘤在形态上具有异质性，细胞结构中位数为 20%（范围为 10%-100%）。 20例中巨核细胞发育不良7例（35%），三系发育不良1例（5%）。经常发生突变的基因包括第二个体细胞 DDX41 突变 (8/19, 42%)，其次是 TET2 (20%)、DNMT3A (20%)、ASXL1 (20%) 和 CUX1 (20%) 突变。 19 例中有 17 例 (89%) 的核型不复杂。结论：本报告扩展了 DDX41 突变疾病的范围，包括 CCUS、T-LGL 和浆细胞疾病。形态学特征具有异质性和非特异性，凸显了 DDX41 检测在血淋巴肿瘤常规检查中的重要性。
Objectives: This study seeks to further characterize the clinicopathologic spectrum of DDX41-mutated hematolymphoid malignancies.Methods: We identified DDX41 mutations from a cohort of known or suspected hematologic disorders and reviewed the corresponding clinical, genetic, phenotypic, and morphologic findings.Results: DDX41 mutations were identified in 20 (1.4%) of 1,371 cases, including 8 cases of acute myeloid leukemia (AML), 5 cases of myelodysplastic syndrome (MDS), 2 cases of therapy-related MDS/AML, 1 case of primary myelofibrosis, 1 case of chronic myeloid leukemia, 1 case of clonal cytopenia of uncertain significance (CCUS), 1 case of T-cell large granular lymphocytic leukemia (T-LGL), and 1 case of multiple myeloma. DDX41-mutated neoplasms were morphologically heterogeneous with a median cellularity of 20% (range, 10%-100%). Megakaryocyte dysplasia occurred in 7 (35%) of 20 cases and trilineage dysplasia in 1 (5%). Frequently comutated genes include a second, somatic DDX41 mutation (8/19, 42%) followed by mutations in TET2 (20%), DNMT3A (20%), ASXL1 (20%), and CUX1 (20%). Karyotypes were noncomplex in 17 (89%) of 19.Conclusions: This report extends the spectrum of DDX41-mutated disorders to include CCUS, T-LGL, and plasma cell disorders. The morphologic features are heterogeneous and nonspecific, highlighting the importance of DDX41 testing during routine workup of hematolymphoid neoplasms.