[Clinicopathological features and gene phenotypes of benign metastasizing leiomyoma].

Objective: To study the clinicopathological features, immunophenotypes and MED12 gene status in benign metastasizing leiomyoma (BML). Methods: Nine cases of BML diagnosed at the Affiliated Hospital of Qingdao University from 2012 to 2018 were collected, and the radiologic and histologic features were analyzed. The protein expression of leiomyosarcoma-related driver genes, including RB1, PTEN,ATRX,p16,p53, as well as ER,PR,CD34,FH, and Ki-67 were detected using immunohistochemistry, and the mutation status of MED12 gene exon 2 was detected by Sanger sequencing. Results: All the nine patients with BML were female, and the age range was 48 to 64 years (median 55 years). All patients had history of uterine fibroids. The morphologic features of BML were similar to a benign uterine leiomyoma and did not exhibit malignant characteristics. All cases were positive for ER and PR, and negative for CD34. In addition, RB1, PTEN, ATRX, and FH were positive in all cases (wild type), while p16 showed a focally positive pattern. P53 positive index was less than 5% (wild type), and Ki-67 positive index was less than 1%. Sanger sequencing was done in six BML samples; one sample harbored a nonsense mutation c. 142_144delinsTAA (p.Glu48Ter), and another exhibited a synonymy mutation (c.192C>T, p.Phe64=)and one missense mutation c.196C>T (p.Pro66Ser). Conclusions: The present study suggests that BML is a unique leiomyoma entity that is pathologically and genetically different from leiomyosarcomas and conventional uterine leiomyomas. Evaluating the genetic phenotype of BML, especially the expression of leiomyosarcoma-related driver genes protein and MED12 gene status, may be helpful in understanding the pathogenesis of BML and in its differentiation from leiomyosarcoma.目的： 探讨良性转移性平滑肌瘤（benign metastasizing leiomyoma，BML）的临床病理学特点、免疫表型及MED12基因突变情况。 方法： 收集青岛大学附属医院2012—2018年的9例BML患者资料，分析影像学资料及组织学形态，采用免疫组织化学EliVision法检测RB1、PTEN、ATRX、p16、p53等常见肿瘤驱动基因蛋白表达以及雌激素受体（ER）、孕激素受体（PR）、CD34、延胡索酸水化酶（FH）、Ki-67等指标的表达情况，采用Sanger测序检测MED12基因第2外显子突变情况。 结果： 9例BML患者均为女性，年龄48~64岁，中位年龄55岁。所有患者均有子宫平滑肌瘤病史。镜下肿瘤细胞形态类似子宫良性平滑肌瘤，不具有恶性组织学特征。肿瘤细胞均表达ER和PR而不表达CD34，RB1、PTEN、ATRX、FH均为阳性（野生型），p16局灶阳性，p53阳性率均<5%（野生型），Ki-67阳性指数均<1%；6例BML标本行Sanger测序，1例存在无义突变c.142_144delinsTAA（p.Glu48Ter），1例同时存在同义突变c.192C>T（p.Phe64=）和错义突变c.196C>T（p.Pro66Ser）。 结论： BML病理组织学及基因表型不同于平滑肌肉瘤以及普通子宫平滑肌瘤，进一步明确BML的基因表型，特别是肿瘤驱动基因蛋白表达及MED12基因突变情况，有助于明确BML的病理机制，辅助其与平滑肌肉瘤的鉴别诊断。.