延胡索酸水合酶缺陷型子宫平滑肌瘤的临床病理分析

Clinicopathologic analysis of fumarate hydratase deficient uterine leiomyoma

目的探讨延胡索酸水合酶(FH)缺陷型子宫平滑肌瘤的临床及组织病理学特征、免疫组织化学特点、诊断及鉴别诊断情况。方法选取2019年1月至2023年9月于首都医科大学附属北京妇产医院就诊的FH缺陷型子宫平滑肌瘤患者66例,收集其临床资料,对所有病例进行FH及2-琥珀酸-半胱氨酸(2SC)免疫组织化学检测,同时分析其临床特征、组织病理学特征、免疫组织化学特点以及分子遗传学检测结果。同时对国内外报道的FH缺陷型子宫平滑肌瘤病例进行文献复习。结果66例患者年龄25~60岁,中位年龄38岁。手术方式包括40例(60.6%)进行子宫肌瘤剔除术,12例(18.2%)进行子宫肌瘤旋切术,14例(21.2%)进行子宫全切术。肿瘤最大径0.7~9.5 cm,65.2%(43/66)为多发性结节。镜下观察到64例表现出鹿角样的血管,58例可见局限或弥漫分布的奇异核细胞,60例出现间质疏松水肿、呈“肺泡样”改变,64例核仁明显、伴核周空晕,65例细胞胞质嗜酸性红染、可见嗜酸性小体,仅1例可见血管外皮瘤样改变;其中1例为起源于FH缺陷型子宫平滑肌瘤的子宫平滑肌肉瘤,核分裂象达11个/10HPF,其余65例核分裂象为(0~6)个/10HPF。大体观察切面大多数为灰白质韧,部分切面呈灰黄色,部分切面有胶冻感。免疫组织化学染色66例肿瘤FH表达均缺失,59例2SC呈强阳性表达(另7例为院外会诊病例,未加做免疫组织化学2SC染色)。15例于外院进行分子遗传学检测,结果显示4例出现体系突变,1例出现胚系突变。随访至2024年4月,患者均健在,且经复查后未出现转移。结论FH缺陷型子宫平滑肌瘤往往具有比较独特的组织学形态,但对于形态学不典型的患者,FH联合2SC的免疫指标组合有助于提高诊断率,必要时仍需结合临床特征以及FH基因突变检测。

Objective To investigate the clinicopathological,histopathological,immunohistochemical,diagnosis and differential diagnosis of fumarate hydratase(FH)deficient uterine leiomyoma.Method 66 cases of FH deficient uterine leiomyoma diagnosed in Beijing Gynecology and Gynecology Hospital of Capital Medical University from January 2019 to September 2023 were collected.Relevant data of the patients were collected.Immunohistochemical detection of FH and S-(2-succino)-cysteine(2SC)were performed in all cases.At the same time,the clinical characteristics,morphology,immunohistochemistry and other characteristics were analyzed and studied.At the same time,the literature of FH deficient uterine leiomyoma reported at home and abroad was reviewed and studied.Result The age of 66 patients was 25-60 years old,the median age was 38 years old.Methods of operation:40 cases of myomectomy,12 cases of myomectomy,14 cases of total hysterectomy.65.2%(43/66)were multiple tumors with a maximum diameter of 0.7-9.5 cm.Under microscope,antler blood vessels(64 cases),pseudoacinoid interstitial edema(60 cases),with strange nuclei(58 cases),cytoplasmic deposits of eosinophilic round hyaloid glomeruli(65 cases),and the eosinophilic nucleoli and surrounding halos(64 cases)were observed,only 1 case showed hemangiopericytoma-like structure.The number of mitotic images(0-6)was 10HPF,but one of them was uterine leiomyosarcoma of FH deficient leiomyoma with 11 mitotic images per 10HPF.General view:Most of the sections are gray-white matter tough,some sections are grayish yellow,and some sections have a gelatinous feeling.Immunohistochemical phenotype:FH expression was missing in 66 tumors,and 2SC expression was strongly positive in 59 tumors(7 cases were consultation cases,and immunohistochemical 2SC was not added).Molecular detection results:15 of them underwent molecular detection,4 cases showed system mutation,1 case showed germ line mutation.Follow-up:All patients survived.Conclusion FH deficient uterine leiomyoma often has unique histological morphology,but for cases with atypical morphology,the combination of FH and 2SC immune indicators can help to improve the diagnosis rate of the disease,and clinical characteristics and FH gene mutation detection should be combined when necessary.