Department of Pathology, Weill Cornell Medicine, New York, New York, USA.
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Pathobiology. 2024;91(1):89-98. doi: 10.1159/000530431. Epub 2023 Mar 30.
The incidence of myelodysplastic syndrome and acute myeloid leukemia is significantly increased in children with Down syndrome (DS). Within the revised 2016 WHO edition, these entities are jointly classified as myeloid leukemia associated with DS (ML-DS). Additionally, infants with DS may develop transient abnormal myelopoiesis (TAM) which is histomorphologically similar to ML-DS. While TAM is self-limiting, it is associated with an increased risk of subsequently developing ML-DS. Differentiating TAM and ML-DS is challenging but clinically critical.
We performed a retrospective review of ML-DS and TAM cases collected from five large academic institutions in the USA. We assessed clinical, pathological, immunophenotypical, and molecular features to identify differentiating criteria.
Forty cases were identified: 28 ML-DS and 12 TAM. Several features were diagnostically distinct, including younger age in TAM (p < 0.05), as well as presentation with clinically significant anemia and thrombocytopenia in ML-DS (p < 0.001). Dyserythropoiesis was unique to ML-DS, as well as structural cytogenetic abnormalities aside from the constitutional trisomy 21. Immunophenotypic characteristics of TAM and ML-DS were indistinguishable, including the aberrant expression of CD7 and CD56 by the myeloid blasts.
The findings of the study confirm marked biological similarities between TAM and ML-DS. At the same time, several significant clinical, morphological, and genetic differences were observed between TAM and ML-DS. The clinical approach and the differential diagnosis between these entities are discussed in detail.
唐氏综合征（Down syndrome，DS）患儿中骨髓增生异常综合征和急性髓系白血病的发病率显著增加。在 2016 年修订版世界卫生组织（World Health Organization，WHO）分类中，这些实体被共同归类为与 DS 相关的髓系白血病（myeloid leukemia associated with DS，ML-DS）。此外，DS 婴儿可能发生短暂性髓系增生异常（transient abnormal myelopoiesis，TAM），其组织形态学与 ML-DS 相似。虽然 TAM 是自限性的，但它与随后发生 ML-DS 的风险增加有关。区分 TAM 和 ML-DS 具有挑战性，但在临床上至关重要。
我们对来自美国五所大型学术机构的 ML-DS 和 TAM 病例进行了回顾性研究。我们评估了临床、病理、免疫表型和分子特征，以确定鉴别标准。
共确定了 40 例病例：28 例 ML-DS 和 12 例 TAM。一些特征具有明显的诊断意义，包括 TAM 中年龄较小（p < 0.05），以及 ML-DS 中存在明显的贫血和血小板减少症（p < 0.001）。除了 21 号染色体三体以外，病态造血是 ML-DS 的特有表现，还有结构细胞遗传学异常。TAM 和 ML-DS 的免疫表型特征无法区分，包括髓系白血病细胞异常表达 CD7 和 CD56。
研究结果证实了 TAM 和 ML-DS 之间存在明显的生物学相似性。同时，在 TAM 和 ML-DS 之间观察到了一些显著的临床、形态学和遗传差异。详细讨论了这些实体的临床方法和鉴别诊断。
