Despite advances in diagnosis of erythrocytosis and thrombocytosis due to driver mutation testing, many cases remain classified as “idiopathic”. This can be explained by the absence of an evident secondary cause, inconclusive bone marrow biopsy or neglection of family history. Analysis of a broad panel of genes through next-generation sequencing (NGS) could improve diagnostic work-up identifying underlying genetic causes. We reviewed the results of NGS performed in our laboratory and its diagnostic impact on 117 patients with unexplained erythrocytosis and 58 with unexplained thrombocytosis; six patients (5.1%) were diagnosed with polycythaemia vera (PV) and 8 (6.8%) with familial erythrocytosis after NGS testing. Low EPO and a family history seemed to predict a positive result, respectively. However, a greater percentage of patients were ultimately diagnosed with secondary erythrocytosis (36%), remained as idiopathic (28.2%) or were self-limited (15%). The yield of NGS was shown to be slightly higher in patients with thrombocytosis, as 15 (25.9%) were diagnosed with essential thrombocythemia (ET) or familial thrombocytosis after variant detection; previous research has shown similar results, but most of them carried out NGS retrospectively, while the present study exhibits the performance of this test in a real-world setting. Overall, the low rate of variant detection and its poor impact on diagnostic work-up highlights the need for a thorough screening prior to NGS, in order to improve its yield.
尽管驱动基因突变检测已提升了红细胞增多症与血小板增多症的诊断水平，但仍有大量病例被归类为“特发性”。这一现象可归因于缺乏明确的继发性病因、骨髓活检结果不确定或家族史被忽视。通过新一代测序技术对广泛基因组合进行分析，可优化诊断流程并识别潜在的遗传学病因。本研究回顾了本实验室对117例不明原因红细胞增多症及58例不明原因血小板增多症患者实施新一代测序的结果及其诊断价值：经检测，6例（5.1%）确诊为真性红细胞增多症，8例（6.8%）诊断为家族性红细胞增多症。低促红细胞生成素水平与家族史分别对阳性结果具有预测价值。然而，最终诊断为继发性红细胞增多症（36%）、维持特发性诊断（28.2%）及自限性病例（15%）的患者占比更高。在血小板增多症患者中，新一代测序的诊断效能略高——变异检测后15例（25.9%）确诊为原发性血小板增多症或家族性血小板增多症；既往研究虽呈现相似结果，但多采用回顾性新一代测序分析，而本研究展示了该技术在真实临床环境中的实际应用效能。总体而言，变异检出率偏低及其对诊断流程改善有限的结果提示，实施新一代测序前需进行系统筛查以提升其诊断价值。
肿瘤(癌症)患者之家