延胡索酸水化酶缺陷型子宫平滑肌瘤5例临床病理及分子遗传学特征  

Clinicopathological and molecular genetic features of fumarate hydratase-deficient uterine leiomyoma:report of five cases

作　　者：付文静[1] 王玉香[1] 吴会芳[1] 胡桂明[1] 冯怡锟[1] 张敏[1] 任景丽[1] FU Wen-jing;WANG Yu-xiang;WU Hui-fang;HU Gui-ming;FENG Yi-kun;ZHANG Min;REN Jing-li(Department of Pathology,the Second Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]郑州大学第二附属医院病理科,郑州450000

出　　处：《诊断病理学杂志》2023年第3期253-256,共4页Chinese Journal of Diagnostic Pathology

摘　　要：目的探讨延胡索酸水化酶(FH)缺陷型平滑肌瘤临床病理特征和分子遗传学特征。方法收集患者的临床相关资料,观察镜下特征,使用免疫组化的方法检测其FH等蛋白的表达情况,并用NGS分子测序的方法检测FH基因的体细胞突变。结果患者平均年龄35岁,5例均无遗传性平滑肌瘤病和肾细胞癌综合征(HLRCC)的典型临床表现。2例FH缺陷型平滑肌瘤呈编织状或束状排列,细胞中-重度的异型性,核分裂象均<5/HPF,有明显的紫红色核仁,3例有鹿角样血管/血管外皮瘤样形态,2例有核内透明小球,可见较多散在分布的瘤巨细胞,间质黏液样变不明显。2例分子遗传学检测均提示FH基因体细胞突变,分别显示FH基因2号外显子c.193G>A(p.Asp65Asn)错义突变及FH基因的7号外显子c.943delc(L315del)移码突变。结论通过FH免疫组化可以发现FH缺陷型平滑肌瘤,借助于组织学表现、FH免疫组化标记有助于临床对HLRCC综合征的诊断,但仍需结合典型的临床表现以及FH基因突变检测。Objective To investigate the clinicopathological and molecular genetic features of fumarate hydratase(FH)-deficient leiomyomas.Methods The clinical data of the patients were collected,their morphological changes were observed,the expression of FH protein and other related proteins in leiomyoma was detected by immunohistochemistry,and the somatic mutation of FH gene was detected by NGS molecular sequencing.Results The average age of the patients was 35 years,and none of the 5 patients had typical clinical manifestations of hereditary leiomyomatosis and renal cell carcinoma(HLRCC)syndrome.Histologically,2 cases of FH-deficient leiomyomas were arranged in braided or fascicular patterns,with moderate-to-severe cellular atypia,mitotic figures 5/HPF,prominent purple-red nucleoli,and 3 cases with antler-like vessels/hemangiopericytoma-like morphology,2 cases had intranuclear transparent globules,and many scattered tumor giant cells were seen,and the interstitial myxoid was not obvious.Molecular genetic testing was performed on 2 cases,both of which suggested somatic mutation of FH gene,which showed missense mutation of exon 2 of FH gene c.193G>A(p.Asp65Asn)and exon 7 of FH gene c.943delc(L315del)frameshift mutation.Conclusion FH-deficient leiomyomas can be screened by FH immunohistochemistry and have unique pathological features.New somatic mutation sites have been found in molecular genetics.With the help of histological manifestations,FH immunohistochemical markers can help in the clinical screening of HLRCC syndrome,but it still needs to be combined with typical clinical manifestations and germline mutation detection of FH gene.

关 键 词：延胡索酸水化酶 平滑肌瘤 临床病理 分子病理学 

分 类 号：R365[医药卫生—病理学]