延胡索酸水合酶缺失型子宫平滑肌瘤38例患者的多中心回顾性研究

Multicenter retrospective study of 38 cases with fumarate hydratase deficiency uterine leiomyoma

目的探讨延胡索酸水合酶(FH)缺失型子宫平滑肌瘤的临床病理特征,并分析影响其术后复发的相关因素。方法收集2015年1月至2021年8月福建省16所省、市级医院接受手术治疗的FH缺失型子宫平滑肌瘤患者共38例,采用免疫组化法检测肌瘤组织中FH、2-琥珀酸-半胱氨酸(2SC)、结蛋白(desmin)、p16、p53、CD_(10)、细胞增殖相关核抗原(Ki-67)蛋白的表达;回顾性分析其临床病理特征。38例患者均随访术后复发情况,中位随访时间为24.5个月(6~76个月);分析影响术后复发的相关因素。结果(1)临床特点:38例FH缺失型子宫平滑肌瘤患者的年龄为(42.5±7.4)岁,多数(21例,55%)为体检发现肌瘤,肌瘤最大径为6.0 cm(5.0~7.5 cm);手术方式:行肌瘤剔除术23例(61%),子宫全切除±双侧附件切除术15例(39%);手术途径:腹腔镜手术27例(71%),开腹手术11例(29%);随访期内患者均未发现患有肾细胞癌。(2)病理特征:常规病理检查镜下观,非典型性核细胞呈局灶或弥漫分布,可见嗜酸性核仁及核内包涵体,胞质内见玻璃样小球,核分裂数0~4个/10个高倍镜视野(HPF),间质内见鹿角状血管及肺水肿样改变。免疫组化法检查显示,38例患者中,FH蛋白阴性表达37例(97%),阳性表达1例(3%);2SC、desmin、p16、p53、CD_(10)、Ki-67阳性表达38例(100%),其中Ki-67指数<10%者35例(92%)、≥10%者3例(8%)。(3)术后复发及其影响因素分析结果:38例患者中,随访期内复发4例,复发率为11%,无死亡患者。年龄、家族肿瘤史、非典型性核分布范围、核分裂数与FH缺失型子宫平滑肌瘤患者术后的复发率均显著相关(P均<0.05)。结论FH缺失型子宫平滑肌瘤是罕见肿瘤,其诊断需病理检查、免疫组化法检测并结合临床病史。当患者年龄<43岁、有家族肿瘤史、非典型性核弥漫分布、核分裂数≥3个/10 HPF时,需警惕其复发风险。

Objective To investigate the clinicopathological features of fumarate hydratase(FH)deficiency uterine leiomyoma.Methods The data of 38 patients with FH deficiency uterine leiomyoma were screened and analyzed.The expressions of FH,S-(2-succino)-cysteine(2SC),desmin,p16,p53,CD_(10) and cell proliferation associated nuclear antigen(Ki-67)proteins were detected by immunohistochemistry,and their clinicopathological features were analyzed retrospectively.Results(1)Clinical features:the median age of the patients was(42.5±7.4)years old.Twenty-one cases(55%)of them were myomas found in physical examination,and the median maximum diameter of the tumor was 6.0 cm(range:5.0-7.5 cm);myomectomy was performed in 23 cases(61%),total hysterectomy with or without bilateral appendages in 15 cases(39%);laparoscopic surgery in 27 cases(71%),open surgery in 11 cases(29%);none of the patients had renal cell carcinoma.(2)Histological features:atypical nuclear cells were distributed locally or diffusely,eosinophilic nucleoli and intranuclear inclusion bodies could be seen,glass like globules could be seen in the cytoplasm,nuclear division was 0-4/10 high power field(HPF),and antler like blood vessels and pulmonary edema-like changes could be seen in the stroma.Among 38 patients with FH deficiency uterine leiomyoma,FH was negative in 37 cases(97%),and positive in 1 case(3%);2SC,desmin,p16,p53,CD_(10) and Ki-67 showed focal positive expression in 38 cases(100%),including 35 cases(92%)with Ki-67 index<10%and 3 cases(8%)with Ki-67 index≥10%.(3)Follow-up:4 cases(11%)recurred,and there was no death.There were significant differences in age,family history,distribution of atypical nuclei and mitosis number between recurrent group and non-recurrent group(all P<0.05).Conclusions FH deficiency uterine leiomyoma is a rare tumor,which needs pathological examination,immunohistochemical examination and clinical history.Patients younger than 43 years old,with family history,histologically atypical diffuse nuclear distribution and mitotic number≥3/10 HPF should be alert to the risk of recurrence.