摘要
目的探讨延胡索酸水合酶(FH)缺陷型子宫平滑肌瘤的临床病理特征、分子遗传学特点及术后复发的关联因素。方法应用免疫组化技术检测郑州大学第三附属医院2020年7月至2022年7月诊断为“伴有奇异核的子宫平滑肌瘤”中FH的表达,筛选出29例FH免疫组化完全阴性表达的病例;应用聚合酶链反应(PCR)及测序技术对其进行FH基因突变检测,共4例发生FH突变,符合FH缺陷型子宫平滑肌瘤。同时对国内外报道的FH缺陷型子宫肌瘤病例进行文献回顾,纳入临床资料完整并有随访数据的病例共62例,总结其术后复发的关联因素。结果发病者年龄为(36.00±4.00)岁,以多发的子宫肌瘤伴有异常子宫出血为最常见症状。肿瘤切面灰白、灰黄色,大部分区域质软。肿瘤细胞具有轻-重度不典型性,缺乏活跃的核分裂像,可见薄壁鹿角状血管,散在奇异形核及多核细胞,细胞核增大,突出的嗜酸性大核仁及核周空晕。免疫组化结果:肿瘤细胞FH表达缺失。本院病例分子遗传学检测结果:1例示4号外显子发生了胚系突变c.395T>G,c.396A>G(体+胚);1例示10号外显子的c.1475T>A错义突变(因无法获得患者的外周血标本,所以无法明确该突变是否为胚系突变);1例FH基因发生体系和胚系c.132+1 G>A突变;另1例示胚系c.191dupA(P.Asn64Lysfs*2)疑似致病变异。年龄<43岁、有家族肿瘤史、肿瘤直径<5 cm、手术方式为单纯子宫肌瘤剥除术的患者肿瘤复发率高(P<0.05)。结论FH缺陷型子宫平滑肌瘤具有其独特的形态学及免疫组化特点,联合检测有助于遗传性平滑肌瘤病和肾细胞癌综合征的筛查,但确诊还需要进行FH基因检测。
Objective To investigate the clinicopathological and molecular genetic characteristics of fumarate hydratase(FH)defective uterine leiomyoma and the associated factors of postoperative recurrence.Methods The expression of FH in uterine leiomyoma with strange nuclei was detected by immunohistochemistry in the Third Affiliated Hospital of Zhengzhou University from July 2020 to July 2022.Twenty-nine cases with completely negative expression of FH were screened out.FH gene mutation was detected by polymerase chain reaction(PCR)and sequencing technology.A total of 4 cases had FH mutation,which was consistent with fumarate hydratase defective uterine leiomyoma.At the same time,the literature of FH defective uterine fibroids reported at home and abroad was reviewed.A total of 62 cases with complete clinical data and follow-up data were included,and the associated factors of postoperative recurrence were summarized.Results The age of the patients was(36.00±4.00)years old,with multiple uterine fibroids accompanied by abnormal uterine bleeding as the most common symptom.The cross-section of the tumor was gray and grayish yellow,and most areas were soft.The tumor cells were characterized by mild to severe atypia,lack of active mitotic images,thin-wall antler vessels,scattered exotic nuclei and multinucleated cells,enlarged nuclei,prominent large eosinophilic nucleoli and perinuclear halos.Immunohistochemical results showed FH expression was absent in tumor cells.The results of molecular genetic examination of the cases in our hospital were as follows.One case showed that exon 4 had a germ line mutation c.395T>G,c.396A>G(body+embryo).One case showed c.1475T>A missense mutation in exon 10(because peripheral blood samples of the patient could not be obtained,it was not clear whether the mutation was a germ line mutation).In one case,FH gene genetic system and embryo line c.132+1 G>A were mutated.Another case showed a suspected pathogenic mutation in germ line c.191dupA(P.Asn64Lysfs*2).Patients with age<43 years old,family hist
作者
李迎宾
董杏
朱换
班振英
张威
杜艳敏
郭永真
陈欣岩
曾宪旭
LI Yingbin;DONG Xing;ZHU Huan;BAN Zhenying;ZHANG Wei;DU Yanmin;GUO Yongzhen;CHEN Xinyan;ZENG Xianxu(Department of Pathology,the Third Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)
出处
《河南医学研究》
CAS
2023年第12期2119-2123,共5页
Henan Medical Research
基金
河南省医学科技攻关计划联合共建项目(LHGJ20210450)。
