心脏/肺动脉未分化(内膜)肉瘤中MDM2的表达及临床病理分析

Expression of MDM2 in cardiac/pulmonary artery undifferentiated(intimal)sarcoma and clinicopathological observation

目的探讨心脏/肺动脉未分化(内膜)肉瘤的临床病理学特征、鉴别诊断及MDM2基因的表达。方法回顾性分析华中阜外医院病理科2018年1月~2019年12月诊治的7例原发于心脏及肺动脉肉瘤的临床病理学特征、免疫表型等,FISH检测MDM2基因扩增,并复习相关文献。结果7例心脏/肺动脉肉瘤中,男性4例,女性3例,患者发病年龄33~67岁,中位年龄52岁,平均44岁。临床症状主要为间断胸闷,其中1例为突发心源性休克。7例中6例行肿物根治切除术,1例行肿物活检术。镜下见肿瘤组织均由非典型梭形和(或)多形性细胞组成,部分区域伴有黏液样或上皮样形态,分化差的区域出现胞体大的单核及多核瘤巨细胞。免疫表型:vimentin弥漫阳性,CD68、Ostonection、MyoD1和desmin均阴性。3例内膜肉瘤MDM2阳性,1例阴性,4例FISH检测MDM2基因扩增,另外3例MDM2阴性或散在阳性且FISH检测MDM2基因阴性诊断为未分化肉瘤。结论原发性心脏/肺动脉的未分化肉瘤和内膜肉瘤是起源于多潜能间充质细胞的恶性肿瘤,临床预后极差,两者肿瘤细胞形态特征相同,免疫组化均无特异性分化标记,通过分子病理检测MDM2基因扩增鉴别内膜肉瘤,有可能使患者从靶向MDM2的小分子拮抗剂的治疗中获益。

Purpose To investigate the clinic-pathological features,diagnosis,differential diagnosis and MDM2 expression of cardiac/pulmonary artery undifferentiated(intimal)sarcoma.Methods The clinical and pathologic features,immunophenotyped of 7 cases of cardiac/pulmonary artery sarcoma,colleted from Fuwai Central China Cardiovascular Hospital from January 2018 to December 2019,were retrospectively analyzed,and fluorescence in situ hybridization(FISH)was preformed to observe MDM2 gene.A literatures review was also performed.Results Among the 7 patients with cardiac/pulmonary artery sarcoma,there were 4 males and 3 females,the age range was 33-67 years,the median age was 52 years,and the average age was 44 years.The main clinical symptoms were intermittent chest distress,in which 1 case was sudden cardiogenic shock.Among the 7 specimens,6 were treated by radical resection and 1 by biopsy.The tumor were composed of atypical spindle and/or pleomorphic cells and was partly mucoid or epithelioid morphology.Large monocytes and multinucleated giant cells were found in the poorly differentiated areas.Immunohistochemical(IHC)staining showed that the tumor tissue was positive for vimentin,CD68,Ostonection,MyoD1,desmin were negative.Among the 4 cases diagnosed as endometrial sarcoma,3 cases were positive for MDM2 by IHC and FISH showed MDM2 gene amplification,1 case was negative for MDM2 by IHC but FISH showed MDM2 gene amplification.The other 3 cases were MDM2 negative by IHC and FISH which were diagnosed as undifferentiated sarcoma.Conclusion Primary cardiac/pulmonary artery undifferentiated(endometrial)sarcoma are malignant tumors with poor prognosis which derived from multipotential mesenchymal cells.Both of them have the same morphological characteristics and there was no specific differentiation marker in immunohistochemistry.However,detection of MDM2 expression can easily detect intimal sarcoma,which may benefit from therapies targeting small molecular antagonists.