[Fumarate hydratase deficient uterine leiomyoma: a clinicopathological and molecular analysis of 80 cases].

Objective: To investigate the clinicopathologic and molecular characteristics of fumarate hydratase (FH) deficient uterine leiomyoma. Methods: Eighty cases of FH deficient uterine leiomyoma were diagnosed from April 2018 to September 2022 in Department of Pathology, Peking University Third Hospital. Sanger sequencing of FH gene exons (exon 1-10) were performed on tumor tissues and matched non-tumor tissues/peripheral blood for all cases. FH immunohistochemistry were performed in 74 cases; S-(2-succino)-cysteine (2SC) were also detected by immunohistochemistry in five cases. Results: Patients' age ranged from 18 to 54 (36.0±7.5) years, with more than 60% exhibiting clinical symptoms of multiple and large leiomyomas (the median diameter was 70 mm). More than four histologic features, including staghorn vasculature, alveolar-pattern edema, bizarre nuclei, oval nuclei arranged in chains, prominent eosinophilic nucleoli with perinucleolar haloes and eosinophilic intracytoplasmic globules were observed in 98.5% (67/68) patients. The immunohistochemical sensitivity of FH and 2SC were 97.3% and 100%, respectively. Based on the Sanger sequencing results, the cases were divided into germline variant group (31 cases), somatic variant group (29 cases) and no variant group (20 cases). Sixty-nine percent (20/29) of the patients with FH germline variation had clear family history. Conclusions: Clinical features, histological morphology, FH and 2SC immunohistochemistry and Sanger sequencing have their own significance and limitations in differential diagnosis of FH deficient uterine leiomyoma. In clinical practice, the above information should be fully integrated and studied for accurate pathologic diagnosis and selection of patients with FH germline variation.目的： 探讨延胡索酸水合酶（fumarate hydratase，FH）缺陷型子宫平滑肌瘤的临床病理及分子遗传学特征。 方法： 收集北京大学第三医院病理科2018年4月至2022年9月诊断的80例FH缺陷型子宫平滑肌瘤，对所有病例肿瘤组织和配对的非肿瘤组织/外周血行FH基因全外显子Sanger测序，对其中74例行FH免疫组织化学检测、5例行2-琥珀酸-半胱氨酸［S-（2-succino）-cysteine，2SC］免疫组织化学检测。 结果： 80例FH缺陷型子宫平滑肌瘤患者18~54岁，平均（36.0±7.5）岁，60%以上有临床症状且肌瘤多发、体积大（最大径中位数为70 mm）。98.5%（67/68）的患者具有4项以上的下列组织学特征：薄壁鹿角样血管、肺泡样水肿、Bizarre核型细胞、链状排列的卵圆形核、突出的嗜酸性核仁、核仁周围空晕和胞质内嗜酸性小体。FH和2SC免疫组织化学的灵敏度分别为97.3%和100%。依据FH基因Sanger测序结果，本组病例被分为胚系变异组（31例）、体系变异组（29例）和未检出变异组（20例）。69.0%（20/29）胚系变异患者有明确家族史。 结论： 临床特征、组织学形态、FH和2SC免疫组织化学及FH Sanger测序对鉴别诊断FH缺陷型子宫平滑肌瘤均有其各自独特的临床意义和局限性，临床实践中应充分整合上述信息并综合判断，才能作出正确的病理诊断并准确遴选出FH基因胚系变异患者。.