Clinicopathological Features And Molecular Mechanism Of Intravenous Leiomyomatosis

Intravenous leiomyomatosis(IVL) is a special kind of uterine leiomyoma, some may extend to inferior vena cava and heart. Beause the clinical manifestations of IVL are various and nonspecific, it is often misdiagnosed, and the subsequent treatment is improper, resulting disastrous consequences, even sudden death.A retrospective analysis of medical records of IVL patients diagnosed in Peking Union Medical College Hospital during 2002 to 2014 was performed to analyze the clinicopathological features and explore the possible relevance to prognosis. Then Affymetrix CytoScan was performed in tumor tissue of IVL and uterine fibroids to investigate the genomic CNV. Immunohistochemical staining was performed in tumor tissue of IVL and uterine fibroids to investigate the expression pattern of ER、PR、 ERBB4、Ki-67、VEGF. We found (1) IVLwith intracaval and intracardiac extension accounted for 56.5% of toal IVL. Approximately 85% of intrapelvic IVL was misdiagnosed to uterine fibroids. Patients that performed surgery of BSO had better prognosis than those who didn’t (P=0.01). whether intrapelvic or extrapelvic(P=0.525), age (P=0.579), size of the pelvic tumor (P=0.352), the preoperative level of CA 125 (P =0.435), the tumor is completely excised or not (P=0.130), hormone therapy (P=0.083) were not significant of prognosis (2) A lot of CNVs exist in tumor tissue of IVL and uterine fibroids.The most frequent recurrent loss of 1 p36.11:MDS2,2 q34:ERBB4,5 q31.1:KIF3a,gain of 1 p36.13:PAX7 were observed in 3 tumors(100%).(3) The protein expression rate of ER、PR in IVL and uterine fibroids are all 100% positive, the range of the positive expression has no significance (P=0.326). The protein expression rate of ERBB4 in IVL and uterine fibroids is 7.7%,0, respectively (P=0.326). Ki-67 index is less than 3% in all cases. High level expression of VEGF in IVL than uterine fibroids (P=0.005).All the above show that the clinical manifestation of IVL is not specific,the rate of misdiagnosed is pretty high (37%). Surgery is the most efficient treatment for IVL,and patients who perform BSO resection have better prognosis. The presence of high frequencies of recurrent regional variation involving several chromosomes is an important finding and likely related to the pathogenesis of IVL. ERBB4, ER,PR, Ki-67, VEGF are not specific marker for IVL. Further investigation of new marker for the diagnosis of IVL is needed.