Clinicopathological analysis of pseudomyogenic hemangioendothelioma with novel NEDD9::FOSB, ZFP36::FOSB, and...

This study aimed to investigate the molecular genetic characteristics and histomorphological spectrum of pseudomyogenic haemangioendothelioma (PHE) and to summarize its clinicopathological features, treatment, and prognosis. We retrospectively analyzed the clinical data, histological morphology, immunohistochemistry, and molecular findings from next-generation sequencing (NGS) in five PHE cases diagnosed at our institution. In addition, we conducted a systematic review of all PHE cases with detailed data reported in the literature worldwide since its reclassification in 2011. Molecular analysis confirmed FOSB gene rearrangements in all five cases. Three cases harbored novel, previously unreported FOSB fusion types (NEDD9::FOSB, ZFP36::FOSB, LGALS3::FOSB), thereby expanding the molecular spectrum of PHE. Histologically, the case with the NEDD9::FOSB fusion exhibited prominent vascular channels surrounded by tumor cells-a morphological feature not previously described in PHE. Our literature review incorporated 270 PHE cases (including our cohort). The median age at disease onset was approximately 32 years, with a male-to-female ratio of about 3.29:1. The primary tumor site was predominantly the extremities. Immunohistochemistry consistently showed expression of CD31, ERG, FLI1, FOSB, and keratins in tumor cells. Molecular testing confirmed the FOSB genetic alteration. Treatment mainly involved surgical resection, and the overall prognosis was relatively favorable. In conclusion, this study expands the molecular genetic spectrum and histomorphological spectrum of PHE. By integrating our data with a systematic literature review, this study provides a comprehensive overview of the clinicopathological features, immunophenotype, molecular genetics, treatment, and prognosis of PHE, offering valuable insights for accurate diagnosis and understanding of its biological behavior.