Molecular Profiling of Benign Metastasizing Leiomyoma of the Uterus Revealing Unique Novel Therapeutic Targets

Extra-uterine manifestations of benign uterine leiomyoma (fibroids) are rare. Benign metastasizing leiomyoma (BML) comprises an uncommon variant characterized by metastatic lung nodules. The pathologic characteristics for BML are well known in the literature; however, the underlying biology and molecular mechanisms remain poorly understood. We present a case of a 43-year-old woman who presented to the hospital complaining of dyspnea and lower extremity edema. Medical history includes a previous hysterectomy for leiomyomata two years prior. A reduced ejection fraction and right atrium globular filling defect are seen on transthoracic echo (TTE). CT scans of the chest, abdomen, and pelvis reported pelvic mass with an extensive inferior vena cava (IVC) thrombus extending into the right atrium, which was subsequently completely resected. Subsequent histopathology for the thrombus reported intravascular leiomyomatosis (IVL) and pelvic mass reported benign leiomyoma. Two years later, the symptoms recurred, and a chest CT revealed new pulmonary nodules. Subsequent pathology from a biopsy of these nodules was consistent with BML with ER+/PR+ on immunohistochemical staining. Genetic testing showed amplification of JUN, cyclin-dependent kinase 4 (CDK4), and MCL1, and loss of SUFU, AT-rich interaction domain 1A (AR1D1A), RB transcriptional corepressor 1 (RB1), and hepatocyte nuclear factor 1-alpha (HNF1A). The patient deemed to be a poor surgical candidate, and, therefore, she was started on hormonal treatment with leuprolide and letrozole. The disease remained stable upon follow-up at 48 months. Here, we report novel genomic profiling findings for the first time in a patient with a newly diagnosed BML. These findings may suggest molecular evidence that IVL may not be as benign as previously thought. Our study further highlights the value of genetic profiling in the understanding of this tumor's behavior and identification of new patient-specific therapeutic targets.