Greater than 90% of cases of systemic mastocytosis (SM) harbor pathogenic KIT mutations, particularly KITD816V. Prognostically-significant pathogenic KIT mutations also occur in 30-40% of core binding factor-associated acute myeloid leukemia (CBF-AML), but are uncommonly associated with concurrent SM. By comparison, the occurrence of SM in other myeloid neoplasms bearing pathogenic KIT mutations, particularly those with a chronic course, is poorly understood. Review of clinical next-generation sequencing (NGS) performed at our institutions in patients with known or suspected hematologic malignancies over an 8-year period revealed 64 patients with both a pathogenic KIT mutation detected at one or more timepoints and available bone marrow biopsy materials. Patients with KITD816V-mutated myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), or overlap MDS/MPN (n = 22) accounted for approximately one-third of our cohort (34%). Comprehensive morphologic and immunophenotypic characterization revealed that nearly all cases (n = 20, 91%) exhibited concurrent SM. In contrast, of the 18 patients (28%) with AML and KITD816V, only eight (44%) showed evidence of SM at any point in their disease course (p = 0.0021); of these eight, the AML component was characterized as AML with myelodysplasia-related changes (AML-MRC) in all but one instance (n = 7, 87%). Twelve patients (19%) had pathogenic KIT mutations other than p.D816V, all in the setting of AML (CFB-AML, n = 7; AML, not otherwise specified, n = 2; AML-MRC, n = 1; acute promyelocytic leukemia, n = 1); only two of these patients (17%), both with CBF-AML, exhibited concurrent SM. The remaining 12 patients (19%) had SM without evidence of an associated hematological neoplasm (AHN). For nearly one-third of the 30 SM-AHN patients in our cohort (n = 9, 30%), the SM component of their disease was not initially clinicopathologically recognized. We propose that identification of the KITD816V mutation in patients diagnosed with MDS, MPN, MDS/MPN, or AML-MRC should trigger reflex testing for SM.

中文翻译：

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在骨髓增生异常和/或骨髓增生性肿瘤和急性髓系白血病中检测到 KITD816V 突变并伴有骨髓增生异常相关的变化可预测并发系统性肥大细胞增多症。

超过 90% 的系统性肥大细胞增多症 (SM) 病例带有致病性 KIT 突变，尤其是 KITD816V。预后显着的致病性 KIT 突变也发生在 30-40% 的核心结合因子相关急性髓性白血病 (CBF-AML) 中，但与并发 SM 相关的并不常见。相比之下，对 SM 在其他携带致病性 KIT 突变的髓系肿瘤中的发生，尤其是那些具有慢性病程的肿瘤，知之甚少。对我们机构在 8 年期间对已知或疑似血液系统恶性肿瘤患者进行的临床二代测序 (NGS) 的回顾显示，64 名患者在一个或多个时间点检测到致病性 KIT 突变，并且有可用的骨髓活检材料。患有 KITD816V 突变的骨髓增生异常综合征 (MDS) 的患者，骨髓增生性肿瘤 (MPN) 或重叠 MDS/MPN (n = 22) 约占我们队列的三分之一 (34%)。综合形态学和免疫表型特征显示几乎所有病例 (n = 20, 91%) 都表现出并发 SM。相比之下，在患有 AML 和 KITD816V 的 18 名患者 (28%) 中，只有八名 (44%) 在其病程的任何时间点显示 SM 的证据 (p = 0.0021)；在这八种情况中，除了一种情况（n = 7, 87%）外，所有 AML 成分都被描述为伴有骨髓增生异常相关变化的 AML (AML-MRC)。12 名患者 (19%) 具有除 p.D816V 以外的致病性 KIT 突变，均处于 AML 环境中（CFB-AML，n = 7；AML，未另行说明，n = 2；AML-MRC，n = 1；急性早幼粒细胞白血病，n = 1）；这些患有 CBF-AML 的患者中只有两名 (17%) 表现出并发 SM。其余 12 名患者 (19%) 患有 SM，但没有相关血液肿瘤 (AHN) 的证据。对于我们队列中 30 名 SM-AHN 患者中的近三分之一 (n = 9, 30%)，他们疾病的 SM 成分最初并未在临床病理学上得到认可。我们建议在诊断为 MDS、MPN、MDS/MPN 或 AML-MRC 的患者中鉴定 KITD816V 突变应该触发 SM 的反射测试。