原发性心脏血管肉瘤13例临床病理学特征及分子遗传学分析

Primary cardiac angiosarcoma:a clinicopathological and molecular genetic analysis of thirteen cases

目的探讨原发性心脏血管肉瘤(primary cardiac angiosarcoma,PCAS)的临床病理学特征及分子遗传学特点,分析KDR突变与PCAS临床病理特点的相关性。方法选择首都医科大学附属北京安贞医院病理科2007年1月至2021年12月间13例PCAS,分析临床病理特征、诊断、鉴别诊断及预后等,行二代测序,基于所得结果对KDR(VEGFR2)进行免疫组织化学染色,结合国内外文献分析讨论。结果男性8例,女性5例,平均年龄45岁。肿瘤原发于右心房10例、左心房2例、右心室1例。组织学形态以低分化为主(11例),梭形或圆形细胞增生呈实片状,细胞明显异型,核分裂象易见,伴大片坏死;高-中分化2例,可见血管腔形成,5例两种分化构象同时存在。免疫表型上,CD34、CD31、Fli1、ERG及波形蛋白均呈弥漫强阳性,上皮样血管肉瘤广谱细胞角蛋白阳性,Ki-67阳性指数3%~90%不等,且Ki-67阳性指数与血管肉瘤分化程度及分级具有正相关性(P<0.05)。所有病例均经手术治疗,至随访结束,1例存活,2例失访,余10例平均生存期4.6个月。最终对筛选后的7例样本行二代测序,结果KDR与NF1突变的均3例,VEGFR2表达与PCAS分化程度及分级无明显相关性(P>0.05),且VEGFR2的免疫组织化学无法区分PCAS是否发生KDR突变。结论PCAS好发于右心房,组织形态以低分化为主,Ki-67阳性指数有助于肿瘤分化程度及分级的判断。PCAS的发生发展可能与KDR突变所涉及的通路有关,但KDR突变与PCAS临床病理特点无明确相关性,且免疫组织化学染色不能代替基因检测来判断肿瘤是否发生KDR突变。

Objective To investigate the clinicopathological and molecular features of primary cardiac angiosarcoma(PCAS),and to analyze the correlation between KDR mutation and the clinicopathological features of PCAS.Methods Thirteen cases of PCAS were collected at Beijing Anzhen Hospital,Capital Medical University from January 2007 to December 2021.The clinicopathological features,diagnosis,differential diagnosis and outcome were retrospectively analyzed.KDR mutation was detected by next-generation sequencing(NGS)and then the expression of KDR(VEGFR2)was determined by immunohistochemistry(IHC),with review of relevant literatures.Results There were eight males and five females with a mean age of 45 years.The primary tumor was in the right atrium in 10 cases,left atrium in two cases and right ventricle in one case.The histomorphology was mainly poorly differentiated angiosarcoma(11 cases),with highly pleomorphic spindle or round cells in solid sheets,brisk mitotic activity and extensive necrosis.Vascular lumen formation was observed in two cases of high to moderate differentiation,and biphenotypic differentiation was seen in five cases.IHC staining showed CD34,CD31,Fli1,ERG and vimentin were diffusely positive,pan-cytokeratin was positive,Ki-67 index ranged from 3%to 90%,which was positively correlated with the differentiation degree and grade of the PCASs(P<0.05).At the end of follow-up period,one patient was alive,two patients were lost to follow-up,and the remaining 10 patients had an average survival time of 4.6 months.Finally,NGS sequencing was performed on seven samples after screening,and the results showed that KDR and NF1 mutations were both present in three cases.VEGFR2 expression had no significant correlation with the differentiation degree and grade of PCAS(P>0.05),and it was not related to KDR mutation.Conclusions PCASs mainly occur in the right atrium,and are mainly poorly differentiated.Ki-67 index is helpful to assess the degree and grade of tumor differentiation.The occurrence and development of PCAS may be related to the pathway involved in KDR mutation,but KDR mutation has no clear correlation with clinicopathological characteristics of PCAS,and immunohistochemical staining can not replace gene detection to determine whether the tumor had KDR mutation.