Uterine leiomyoma (UL) is a common benign neoplasm which can sometimes be difficult to differentiate from the uterine inflammatory myofibroblastic tumor (IMT) based on morphology alone. IMT is a myofibroblastic/fibroblastic neoplasm which has typically been considered to be rare in the uterus. Its clinical behavior is usually indolent although aggressive variants exist. The majority of IMTs harbor genomic rearrangement ofanaplastic lymphoma kinase(ALK), whileALKfusion has not been thus far detected in ULs. We analyzed 2263 ULs of which 9 (0.4%) had tyrosine-kinase activation. Seven of the samples were ALK immunopositive: 6 had anALKfusion gene and 1 overexpressed anALKtranscript skipping exons 2 to 3, Moreover, 1 sample had aRET, and 1 aPDGFRBfusion gene. While no recurrent somatic mutations were found, 1 patient had anALKgermline mutation. Seven tumors showed leiomyoma-like morphology, 1 tumor had slightly loose, and 1 fibrous growth pattern. Six tumors had mild to moderate lymphocyte infiltration, while no immune cell infiltration was detected in 3 cases. None of the tumors showed aggressive behavior. Except for strong ALK positivity (7/9 tumors) the protein expression profile of the tumors was identical to ULs and distinct from other mesenchymal uterine tumors. In gene expression level, these tumors and the known UL subclasses did not separate perfectly. However, vitamin C metabolism and epithelial-mesenchymal transition pathways were uniquely enriched in these lesions. The overall similarity of the analyzed tumors to UL raises the question whether an UL diagnosis would be more proper for a subset of uterine IMTs.

子宫肌瘤（UL）是一种常见的良性肿瘤，有时仅根据形态很难与子宫炎性肌纤维母细胞瘤（IMT）区分开来。IMT 是一种肌纤维母细胞/成纤维细胞肿瘤，通常被认为在子宫中罕见。尽管存在攻击性变异，但其临床行为通常是惰性的。大多数 IMT 都存在间变性淋巴瘤激酶( ALK ) 的基因组重排，而UL 中尚未检测到ALK融合。我们分析了 2263 个 UL，其中 9 个（0.4%）具有酪氨酸激酶激活。其中 7 个样本呈 ALK 免疫阳性：6 个样本具有ALK融合基因，1 个样本过表达跳过外显子 2 至 3 的ALK转录物，此外，1 个样本具有 RET ， 1个样本具有PDGFRB融合基因。虽然未发现复发性体细胞突变，但 1 名患者存在ALK种系突变。7个肿瘤呈平滑肌瘤样形态，1个肿瘤稍疏松，1个肿瘤呈纤维状生长。6例肿瘤有轻中度淋巴细胞浸润，3例未检测到免疫细胞浸润。没有一个肿瘤表现出攻击性行为。除了强 ALK 阳性（7/9 肿瘤）外，肿瘤的蛋白质表达谱与 UL 相同，并且与其他间叶性子宫肿瘤不同。在基因表达水平上，这些肿瘤与已知的 UL 亚类并没有完美区分。然而，维生素 C 代谢和上皮-间质转化途径在这些病变中独特地丰富。所分析的肿瘤与 UL 的总体相似性提出了一个问题，即 UL 诊断是否更适合子宫 IMT 的子集。