Background

Little is known about the epidemiology of advanced systemic mastocytosis (advSM).

Objectives

To investigate epidemiologic features and diagnostic pitfalls of advSM in Germany.

Methods

Therefore, 140 patients from a single German reference center of the European Competence Network on Mastocytosis between 2003 and 2018 were analyzed.

Results

The patients' median age was 68 years (range, 26-86 years), and male versus female ratio was 2:1. An elevated serum tryptase, a KIT D816 mutation, and additional somatic mutations, for example, in SRSF2, ASXL1, or RUNX1, were identified in 95%, 91%, and 74% of patients, respectively. Median overall survival was 3.5 years (range, 0.03-14.3 years; male vs female 2.6 vs 4.2 years; P = .02). Two categories of misdiagnoses were identified in 51 of 140 (36%) patients: First, systemic mastocytosis (SM) was overlooked in 28 of 140 (20%) patients primarily diagnosed with various subtypes of myeloid neoplasms. Second, 23 of 140 (16%) patients were diagnosed with supposed progression from indolent SM to advSM; however, combination of an elevated KIT D816V variant allele frequency in peripheral blood (n = 22), monocytosis (n = 9), eosinophilia (n = 6), and/or mutations in SRSF2, ASXL1, or RUNX1 (n = 10) suggest that distinct signs of potential advSM were overlooked in virtually all patients. Based on locally diagnosed patients in an area of 2.5 million inhabitants, but obviously without considering more, yet unrecognized cases, the incidence and prevalence of advSM is at least 0.8 and 5.2, respectively, per 1 million inhabitants.

Conclusions

Adequate analyses of tryptase levels, bone marrow morphology, and genetics in patients with myeloid neoplasms or SM would help to prevent the significant underdiagnosis of advSM.

中文翻译：

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正确诊断晚期全身细胞肥大症的适当诊断检查的重要性。

背景

关于晚期全身性肥大细胞增多症（advSM）的流行病学知之甚少。

目标

调查advSM在德国的流行病学特征和诊断陷阱。

方法

因此，分析了2003年至2018年间来自欧洲细胞吞噬作用能力咨询网络的单个德国参考中心的140名患者。

结果

患者的中位年龄为68岁（范围26-86岁），男女之比为2：1。分别在95％，91％和74％的患者中发现血清胰蛋白酶升高，KIT D816突变和其他体细胞突变，例如在SRSF2，ASXL1或RUNX1中。中位总生存期为3.5年（范围：0.03-14.3岁；男性vs女性2.6 vs 4.2岁；P = .02）。在140名患者中有51名（36％）识别出两类误诊：首先，在140名患者中有28名（20％）主要被诊断出患有各种类型的骨髓瘤的患者中，系统性肥大细胞增多症（SM）被忽略。其次，在140例患者中有23例（16％）被诊断出从惰性SM到advSM的预期进展；但是，外周血（n = 22），单核细胞增多症（n = 9），嗜酸性粒细胞增多（n = 6）和/或SRSF2，ASXL1或RUNX1突变的KIT D816V变异等位基因频率升高的组合（n = 10）表明，几乎所有患者都忽略了潜在的advSM的明显体征。基于250万居民中的本地诊断患者，但显然没有考虑更多但尚未发现的病例，每100万居民中advSM的发生率和患病率分别至少为0.8和5.2。

结论

对患有髓样肿瘤或SM的患者中的类胰蛋白酶水平，骨髓形态和遗传学进行充分的分析将有助于防止advSM的严重误诊。