Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Clin Exp Med. 2024 Jul 23;24(1):165. doi: 10.1007/s10238-024-01441-w.
Here, we reviewed clinical-morphological data and investigated mutational profiles by NGS in a single-center series of 28 consecutive patients admitted to our hospital between September 2011 and November 2021 for idiopathic hypereosinophilia (HE).Bone marrow (BM) morphology was evaluated in 22 patients: while in six subjects BM was unremarkable, in the remaining cases an increase in BM eosinophils was observed, together with a slight increase in BM fibrosis (MF-1) in 5/22 patients.A total of 4/28 patients had at least one genetic lesion by targeted NGS. In particular, the genes involved were: two each of TET2 and DNMT3A; and one each of JAK2V617F, ASXL1, PPM1D, and ZBTB33. Notably, JAK2V617F and TET2 mutations co-occurred, with the JAK2V617F-mutated sample also carrying TET2 lesions. Median VAF was 21%, with the exception of the oncodriver JAK2V617F, which showed a VAF > 50% in the reported case. Of note, of the four cases bearing lesions, 2/4 had multiple hits in different genes.While in recent years mutational analysis using NGS has proven to be able to differentiate clonal hematopoietic neoplasms from reactive processes in diagnostically difficult cases, we found somatic mutations in only 14.3% of patients who acceded to our hospital for idiopathic HE. More importantly, excluding the JAK2V617F-mutated case with an underlying MPN-Eo diagnosis, NGS was able to identify somatic mutations in only three cases, all older than 70 years. Consequently, the detection of these mutations in idiopathic HE patients should be interpreted with caution and only in the context of other supportive clinical-pathological findings.
在这里，我们回顾了 2011 年 9 月至 2021 年 11 月期间因特发性嗜酸性粒细胞增多症（HE）连续 28 例在我院住院患者的临床形态学数据，并通过 NGS 研究了突变谱。22 例患者进行了骨髓（BM）形态学评估：6 例患者 BM 无明显异常，其余患者 BM 嗜酸性粒细胞增多，5/22 例患者 BM 纤维化（MF-1）略有增加。共有 4/28 例患者通过靶向 NGS 检测到至少一种基因病变。具体而言，涉及的基因有：TET2 和 DNMT3A 各两个；JAK2V617F、ASXL1、PPM1D 和 ZBTB33 各一个。值得注意的是，JAK2V617F 和 TET2 突变同时发生，JAK2V617F 突变样本还携带 TET2 病变。中位 VAF 为 21%，除报告病例中的驱动基因 JAK2V617F 外，VAF>50%。值得注意的是，在携带病变的 4 例中，有 2/4 例在不同基因中存在多个命中。尽管近年来使用 NGS 的突变分析已被证明能够在诊断困难的病例中区分克隆性造血肿瘤与反应性过程，但我们发现仅在 14.3%因特发性 HE 入院的患者中存在体细胞突变。更重要的是，排除潜在 MPN-Eo 诊断的 JAK2V617F 突变病例，NGS 仅在 3 例年龄大于 70 岁的患者中能够识别体细胞突变。因此，在特发性 HE 患者中检测到这些突变应谨慎解释，并且仅在其他支持性临床病理发现的背景下进行。
