延胡索酸水合酶缺陷型肾癌单中心诊疗经验

Single-center experience with fumarate hydratase-deficient renal cell carcinoma

摘要

目的 探讨延胡索酸水合酶缺陷型肾细胞癌（FH-RCC）疾病特点，总结并分析其诊疗效果。方法 回顾性分析空军军医大学附属西京医院2023年2月-2025年4月收治的10例病理拟诊FH-RCC患者的临床资料，包括患者的性别、年龄、临床症状、影像学、病理学、基因检测、治疗方案及随访结果等。结果 10例患者中，结合病理和基因检测最终确诊FH-RCC 7例，其中6例男性，1例（既往子宫肌瘤病史）女性，年龄25～72岁，其中4例为体检发现，其余因血尿、乏力发现。所有患者均接受手术治疗（肾部分切除术2例，肾根治性切除术5例），平均手术时间207 min，其中2例合并肾静脉或下腔静脉癌栓。术后免疫组化结果提示延胡索酸水合酶（FH）阴性6例，2琥珀酸半胱氨酸（2SC）阳性7例。5例患者行基因检测，其中FH体系突变1例，胚系突变4例，术前新辅助靶向治疗1例，术后辅助治疗（靶向或联合免疫治疗）4例，随访时间10～30个月，复发或转移3例，其中2例给予阿昔替尼+特瑞普利单抗治疗，1例给予伏罗尼布片+卡度尼利+介入治疗，治疗效果良好。结论 FH-RCC是一种临床罕见且具有高度侵袭性的恶性肿瘤，术前确诊困难，目前临床上尚无标准的术后辅助或者晚期FH-RCC治疗方案。针对术后出现转移的患者，给予靶向联合免疫治疗可延缓疾病进展。

Abstract

Objective To investigate the characteristics of fumarate hydratase-deficient renal cell carcinoma（FH-RCC）and analyze its diagnosis and treatment outcomes. Methods A retrospective analysis was conducted on the clinical data of 10 patients initially suspected of FH-RCC and treated in our hospital during Feb. 2023 and Apr. 2025，including gender，age，clinical symptoms，imaging findings，pathology，genetic testing，treatment regimens，and follow-up outcomes. Results Among the 10 patients，7 were finally diagnosed with FH-RCC based on pathological and genetic testing results，including 6 males and 1 female（with a previous history of uterine fibroids），aged 25 to 72 years. Four cases were identified during physical examination，while the others were detected due to symptoms of hematuria and fatigue. Surgical treatment was conducted，including partial nephrectomy in 2 and radical nephrectomy in 5. Two patients were found to be complicated with renal vein or inferior vena cava tumor thrombi. The mean operation time was 207 minutes. Postoperative immunohistochemical results showed negative FH staining in 6 cases and positive succinated cysteine（2SC）staining in 7 cases. Genetic testing was performed in 5 patients，revealing 1 case with somatic FH mutation and 4 cases with germline FH mutation. One patient was treated with preoperative neoadjuvant targeted therapy，and 4 with postoperative adjuvant therapy（targeted therapy or combined immunotherapy）. During the follow-up of 10 to 30 months，recurrence or metastasis occurred in 3 cases，2 of which received axitinib plus toripalimab，and 1 vorolanib plus cadonilimab combined with interventional therapy，all achieving favorable therapeutic responses. Conclusion FH-RCC is a rare and highly aggressive malignant tumor，which is difficult to confirm preoperatively，with no standardized adjuvant or advanced-stage treatment regimen. For patients who develop metastases after surgery，targeted therapy combined with immunotherapy may help delay disease progression.

关键词

延胡索酸水合酶缺陷型肾癌 / 延胡索酸水合酶 / 2琥珀酸半胱氨酸 / 辅助治疗

Key words

fumarate hydratase-deficient renal cell carcinoma / fumarate hydratase / 2-succinocysteine / adjuvant therapy

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