Pathological and molecular insights into intravenous leiomyomatosis: an integrative multi-omics study

Abstract Intravenous leiomyomatosis (IVL) is a histologically well differentiated smooth muscle tumor with aggressive behavior, capable of extending throughout the venous system. Due to its rarity, systematic studies on IVL are limited. We conducted a comprehensive multi-omics study, collecting tissues from IVL, uterine fibroid, and normal myometrium. Single-cell RNA sequencing analysis revealed a significant difference in cell composition between IVL and uterine fibroid. H&E staining demonstrated more frequent hydropic change and hyalinization, with decreased vascular density in IVL tissues compared to both normal myometrium and uterine fibroid. Proteomics analysis in 8 paired IVL and normal myometrium fresh frozen tissue identified differentially expressed proteins mainly enriched in focal adhesions and regulation of the actin cytoskeleton. The most frequently involved chromosomes included deletions in 10q22.2, 10q24.32, 13q14, and 13q21-31. Correlation analyses highlighted chromosome 10q as the most frequent cytoband, with corresponding proteins involved in regulating focal adhesions and the cytoskeleton. Integrated analysis between pathological and clinical characteristics indicated that chromosome 10q deletion and vascular morphology in IVL could serve as important markers predicting aggressive behavior. Our study illuminates the pathological and molecular changes associated with IVL, offering insights that may contribute to establishing new directions for IVL treatment.