Molecular Heterogeneity and Clinicopathologic Correlations in Inflammatory Myofibroblastic Tumors of the Urinary Bladder

作者：Ming Zhao, Xiaoqun Yang, Zhe Zhang, Rong Fang, Jiayun Xu, Huizhi Zhang, Zheng Li, Miaomiao Shen, Suying Wang, Huiying He · 发表于：The American Journal of Surgical Pathology · 年份：2025 · DOI：10.1097/pas.0000000000002477 · 被引用次数：2 · 研究领域：IgG4-Related and Inflammatory Diseases、Neuroendocrine Tumor Research Advances、Gastrointestinal disorders and treatments

Inflammatory myofibroblastic tumors (IMTs) of the urinary bladder are rare mesenchymal neoplasms with an incompletely defined molecular spectrum. This integrated clinicopathologic and molecular study of 20 bladder IMTs utilized immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and targeted RNA sequencing to characterize their molecular drivers. Clinically, patients (mean age 45 y) presented with hematuria (85%) and cystoscopic polypoid/nodular masses; despite muscularis propria invovlement (55%) or perivesical soft tissue extension (5%), clinical outcomes were excellent (90% disease-free survival; mean follow-up 32.6 mo), with 2 recurrences managed by repeat resection. Histologically, the tumors exhibited mixed growth patterns: compact spindle cell (75%), myxoid (50%), and hypocellular fibrous (20%), with 45% showing combined features. IHC revealed ALK positivity in 90% (18/20) of cases, predominantly diffuse cytoplasmic staining (17/18), while keratins (AE1/AE3 and/or CAM5.2) were positive in 83.3%. Molecular analysis identified ALK rearrangements in 87.5% (14/16) of FISH-tested cases (signal separation: 13% to 42%) and gene fusions in 88.9% (16/18) of RNA-sequenced cases, with FN1::ALK being the predominant fusion (75%, 12/16). Rare fusions included VCL::ALK , DCTN1::ALK , PPFIBP1::ALK , and a novel TFG::ROS1 (confirmed by RT-PCR and Sanger sequencing). Distinct genotype-phenotype correlations emerged: myxoid morphology strongly associated with FN1::ALK...