Case Report: Pleomorphic adenoma of the breast: diagnostic pitfalls and a novel PLAG1::FTO fusion

Pleomorphic adenoma (PA) of the breast and its malignant transformation represent extremely rare clinical entities, and the molecular alterations underlying this tumor type remain largely uninvestigated to date. Herein, we report a diagnostic challenge posed by a case of mammary pleomorphic adenoma, which was initially misdiagnosed as mucinous carcinoma during frozen section examination; the definitive diagnosis was ultimately confirmed based on a comprehensive analysis of the surgical resection specimen. As implied by the term “pleomorphic,” this tumor exhibits remarkable phenotypic heterogeneity. Therefore, a thorough understanding of the morphological features of rare breast PA is crucial for mitigating the risk of misdiagnosis in clinical practice. To explore the genetic characteristics of this tumor, we employed High-throughput Chromosome Conformation Capture (Hi-C) and RNA sequencing (RNA-Seq) to detect potential gene rearrangements. Importantly, a novel PLAG1::FTO gene fusion was identified in this case. Our findings not only highlight the diagnostic complexity of this rare breast neoplasm, which is prone to misclassification, but also expand the known genetic landscape of PA through the discovery of the novel PLAG1::FTO fusion. This study thus provides valuable new insights for future molecular research on pleomorphic adenoma.