Abstract：
OBJECTIVE: VEXAS syndrome is an adult-onset autoinflammatory disease caused by a somatic pathogenic mutation in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. Patients present with rheumatologic manifestations and cytopenias and may have an increased predisposition to myelodysplastic syndrome (MDS) and plasma cell neoplasms. Prior studies have reported on the peripheral blood and bone marrow findings in patients with VEXAS syndrome. Due to the protean clinical presentation and lack of specificity of morphologic features (eg, vacuoles in early erythroid and granulocytic precursors), an optimal screening methodology to identify these patients in a timely fashion is desirable.
METHODS: To further evaluate and describe the salient diagnostic morphologic features in VEXAS syndrome, we carried out a comprehensive study of the largest single-institution cohort to date. Diagnostic and follow-up bone marrow biopsy specimens from 52 male patients with molecularly identified VEXAS syndrome underwent central review.
RESULTS: Cytopenias were common in all cases, primarily macrocytic anemia, monocytopenia, and thrombocytopenia. Bone marrow aspirate and biopsy were often hypercellular, with an increased myeloid/erythroid ratio, granulocytic hyperplasia with left shift, erythroid left shift, and megakaryocyte hyperplasia, which exhibited a range of striking morphologic findings. Distinctly vacuolated myeloid and erythroid precursors were seen in more than 95% of cases.
CONCLUSIONS: Our data reveal potential novel diagnostic features, such as a high incidence of monocytopenia and distinct patterns of atypical megakaryopoiesis, that appear different from dysmegakaryopoiesis typically associated with MDS. In our experience, those findings are suggestive of VEXAS, in the appropriate clinical context.
METHODS: To further evaluate and describe the salient diagnostic morphologic features in VEXAS syndrome, we carried out a comprehensive study of the largest single-institution cohort to date. Diagnostic and follow-up bone marrow biopsy specimens from 52 male patients with molecularly identified VEXAS syndrome underwent central review.
RESULTS: Cytopenias were common in all cases, primarily macrocytic anemia, monocytopenia, and thrombocytopenia. Bone marrow aspirate and biopsy were often hypercellular, with an increased myeloid/erythroid ratio, granulocytic hyperplasia with left shift, erythroid left shift, and megakaryocyte hyperplasia, which exhibited a range of striking morphologic findings. Distinctly vacuolated myeloid and erythroid precursors were seen in more than 95% of cases.
CONCLUSIONS: Our data reveal potential novel diagnostic features, such as a high incidence of monocytopenia and distinct patterns of atypical megakaryopoiesis, that appear different from dysmegakaryopoiesis typically associated with MDS. In our experience, those findings are suggestive of VEXAS, in the appropriate clinical context.
摘要：
目的：VEXAS综合征是由UBA1（泛素样修饰物激活酶1）基因的体细胞致病突变引起的成人发作的自身炎症性疾病。患者表现为风湿病表现和血细胞减少症，并且可能对骨髓增生异常综合征（MDS）和浆细胞肿瘤的易感性增加。先前的研究已经报道了VEXAS综合征患者的外周血和骨髓发现。由于蛋白质的临床表现和缺乏形态学特征的特异性（例如，早期红系和粒细胞前体的液泡），需要一种最佳的筛查方法来及时识别这些患者.
方法：为了进一步评估和描述VEXAS综合征的显著诊断形态学特征，我们对迄今为止最大的单机构队列进行了全面研究.对52例具有分子鉴定的VEXAS综合征的男性患者的诊断和随访骨髓活检标本进行了中心审查。
结果：细胞减少症在所有病例中都很常见，主要是大细胞性贫血,单核细胞减少症,和血小板减少症.骨髓穿刺和活检通常是高细胞，随着髓系/红系比率的增加，粒细胞增生左移，红系左移,巨核细胞增生，表现出一系列惊人的形态学发现。在超过95％的病例中看到明显的空泡状髓样和红系前体。
结论：我们的数据揭示了潜在的新诊断特征，例如单核细胞减少症的高发病率和非典型巨核细胞生成的不同模式，似乎不同于通常与MDS相关的巨核细胞生成。根据我们的经验,这些发现暗示了VEXAS，在适当的临床背景下。
方法：为了进一步评估和描述VEXAS综合征的显著诊断形态学特征，我们对迄今为止最大的单机构队列进行了全面研究.对52例具有分子鉴定的VEXAS综合征的男性患者的诊断和随访骨髓活检标本进行了中心审查。
结果：细胞减少症在所有病例中都很常见，主要是大细胞性贫血,单核细胞减少症,和血小板减少症.骨髓穿刺和活检通常是高细胞，随着髓系/红系比率的增加，粒细胞增生左移，红系左移,巨核细胞增生，表现出一系列惊人的形态学发现。在超过95％的病例中看到明显的空泡状髓样和红系前体。
结论：我们的数据揭示了潜在的新诊断特征，例如单核细胞减少症的高发病率和非典型巨核细胞生成的不同模式，似乎不同于通常与MDS相关的巨核细胞生成。根据我们的经验,这些发现暗示了VEXAS，在适当的临床背景下。
