Inflammatory myofibroblastic tumors arising in infants are rare, poorly investigated and mostly reported as isolated cases or as a part of larger series thus, their clinicopathological and molecular features are essentially unknown. Archival files from two large pediatric institutions and a tumor registry were queried for pediatric inflammatory myofibroblastic tumors. Available material from patients ≤12 months of age was reviewed. Additional immunostains (ALK-1, D240, WT1) and ALK-FISH studies were performed as needed. Targeted anchored multiplex PCR with next-generation sequencing was done in all cases. A total of 12 of 131 infantile cases (mean 5.5 months) were identified (M:F of 2:1). Anatomic locations included intestinal/mesenteric (n = 6), head/neck (n = 3), and viscera (n = 3). Half of tumors showed a hypocellular myxoid pattern, perivascular condensation, and prominent vasculature with vague glomeruloid structures present in four of them. The remaining cases exhibited a more cellular pattern with minimal myxoid component. ALK-1 immunohistochemistry was positive in most cases (11/12) with cytoplasmic-diffuse (n = 6), cytoplasmic-granular (n = 2), and dot-like (n = 3) staining patterns. ALK fusion partners identified in five cases included EML4, TPM4, RANBP2, and a novel KLC1. Three inflammatory myofibroblastic tumors showed fusions with other kinases including TFG-ROS1 and novel FN1-ROS1 and RBPMS-NTRK3 rearrangements. Favorable outcome was documented in most cases (10/11) with available follow-up (median 17 months) while three patients were successfully treated with crizotinib. In summary, infantile inflammatory myofibroblastic tumors are rare and can exhibit paucicellular, extensively myxoid/vascular morphology with peculiar immunophenotype mimicking other mesenchymal or vascular lesions. All tumors harbored kinase fusions involving ALK, ROS1, and NTRK3 including three novel fusion partners (KLC1, FN1, and RBPMS, respectively). A favorable response to crizotinib seen in three cases supports its potential use in infants as seen in older patients. Awareness of these unusual morphologic, immunophenotypic, and molecular features is critical for appropriate diagnosis and optimized targeted therapy.

婴儿发生的炎性肌纤维母细胞肿瘤很少见，研究很少，并且大多作为孤立病例或作为较大系列的一部分进行报道，因此，它们的临床病理学和分子特征基本上是未知的。从两个大型儿科机构和一个肿瘤登记处的档案文件中查询了儿科炎症性肌纤维母细胞瘤。审查了 12 个月以下患者的可用材料。根据需要进行额外的免疫染色（ALK-1、D240、WT1）和 ALK-FISH 研究。在所有情况下都进行了具有下一代测序的靶向锚定多重 PCR。确定了 131 例婴儿病例中的 12 例（平均 5.5 个月）（男女比例为 2:1）。解剖位置包括肠/肠系膜（n  = 6）、头/颈（n  = 3）和内脏（n  = 3). 一半的肿瘤显示出低细胞粘液样模式、血管周围凝缩和显着的血管系统，其中四个肿瘤具有模糊的肾小球样结构。其余病例表现出更多的细胞模式，粘液样成分最少。ALK-1 免疫组织化学在大多数情况下 (11/12) 呈阳性，具有细胞质弥漫性 ( n  = 6)、细胞质颗粒状 ( n  = 2) 和点状 ( n  = 3) 染色模式。在五个病例中鉴定出的ALK融合伙伴包括EML4、TPM4、RANBP2和一个新的KLC1。三种炎性肌纤维母细胞肿瘤显示与其他激酶融合，包括TFG-ROS1以及新的FN1-ROS1和RBPMS-NTRK3重排。在大多数病例 (10/11) 中记录了良好的结果并进行了随访（中位 17 个月），同时三名患者成功地接受了克唑替尼治疗。总之，婴儿炎性肌纤维母细胞肿瘤是罕见的，可以表现出细胞稀少、广泛的粘液样/血管形态，具有模仿其他间充质或血管病变的特殊免疫表型。所有肿瘤都含有涉及ALK、ROS1和NTRK3的激酶融合，包括三个新的融合伴侣（KLC1、FN1和RBPMS， 分别）。在三个病例中观察到对克唑替尼的良好反应支持其在婴儿中的潜在用途，如在老年患者中所见。了解这些不寻常的形态学、免疫表型和分子特征对于正确诊断和优化靶向治疗至关重要。