背景:具有RAM免疫表型的急性髓性白血病(AML)是AML的一种独特亚型,正如儿童肿瘤学小组(COG)所描述的那样,具有特征性的形态学和免疫表型特性。它的特点是强烈的CD56表达与暗淡到阴性CD45,HLA-DR,和CD38表达。它是一种侵袭性白血病,对诱导化疗和/或频繁复发反应较差。
方法:对2019年1月至2021年12月初诊儿童AML病例进行回顾性分析,发现7例具有特征性RAM免疫表型。在这里,我们批判性地分析了他们的临床,形态学,细胞化学,免疫表型,细胞遗传学,和分子概况。对患者进行追踪和随访,了解他们目前的疾病和治疗状况。
结果:302例小儿AML(年龄<18岁),观察到7例(2.3%)具有明显的RAM表型,年龄从9个月到5岁不等。2例患者由于CD56阳性和缺乏白细胞共同抗原(LCA),早期误诊为小圆形细胞肿瘤,但后来被正确鉴定为粒细胞肉瘤。骨髓抽吸物显示出具有异常凝聚性和结块的核成型,模仿非血液系统恶性肿瘤。流式细胞术显示母细胞具有低侧向散射,调暗至负CD45和CD38,负cMPO,CD36和CD11b;中度至明亮的CD33,CD117和明亮的CD56。与内部对照相比,CD13表达的平均荧光强度(MFI)显著更低。细胞遗传学和分子研究未显示任何复发性异常。5/7例进行CBFA2T3-GLIS2融合的逆转录聚合酶链反应,有一个积极的结果。在临床随访中,2例患者化疗难治.7例病例中有6例死亡(存活时间:初始诊断后3-343天)。
结论:具有RAM免疫表型的AML,一种不同形式的儿童AML,预后不良,如果表现为软组织肿块,可能会构成诊断挑战。全面的免疫表型评估,包括干细胞和骨髓标志物,对于用RAM免疫表型准确诊断髓系肉瘤至关重要。我们的数据证明弱CD13表达是另外的免疫表型发现。
BACKGROUND: Acute myeloid leukemia (AML) with RAM immunophenotype is a distinct subtype of AML, as described by the Children\'s Oncology Group (COG), with characteristic morphological and immunophenotypic properties. It is characterized by strong CD56 expression with dim to negative CD45, HLA-DR, and CD38 expression. It is an aggressive leukemia with a poor response to induction chemotherapy and/or frequent relapses.
METHODS: Seven cases with the characteristic RAM immunophenotype were identified in this retrospective analysis of newly diagnosed pediatric AML cases from January 2019 to December 2021. Herein, we have critically analyzed their clinical, morphological, cytochemical, immunophenotyping, cytogenetic, and molecular profiles. The patients were traced and followed for their current disease and treatment status.
RESULTS: Of 302 cases of pediatric AML (age <18 years), seven cases (2.3%) with the distinct RAM phenotype were observed, with age ranging from 9 months to 5 years. Two patients were misdiagnosed earlier as small round cell tumor because of the strong CD56 positivity and the absence of leukocyte common antigen (LCA), but they were later correctly identified as granulocytic sarcoma. The bone marrow aspirate showed blasts with unusual cohesiveness and clumping with nuclear moulding, mimicking non-hematologic malignancies. Flow cytometry revealed blasts with low side scatter, dim to negative CD45 and CD38, negative cMPO, CD36, and CD11b; moderate to bright CD33, CD117, and bright CD56. The Mean fluorescence intensity (MFI) of CD13 expression was significantly lower as compared to the internal controls. Cytogenetic and molecular studies did not show any recurrent abnormalities. Reverse transcription polymerase chain reaction for CBFA2T3-GLIS2 fusion was performed in 5/7 cases, with one positive result. On clinical follow-up, two patients were refractory to chemotherapy. Six of the seven cases had succumbed to death (duration of survival: 3-343 days after initial diagnosis).
CONCLUSIONS: AML with RAM immunophenotype, a distinct form of pediatric AML with a poor prognosis, may pose a diagnostic challenge if presented as a soft tissue mass. A comprehensive immunophenotypic evaluation, including stem cell and myeloid markers, is critical for an accurate diagnosis of myeloid sarcoma with the RAM-immunophenotype. Our data demonstrated weak CD13 expression as an additional immunophenotypic finding.