Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant disorder that results from a germline mutation in the fumarate hydratase gene (FH). Individuals with FH mutations are at risk of developing renal cell carcinoma (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is as yet no standardized therapy for advanced HLRCC-RCC. We report an aggressive RCC case in a 49-year-old man. Nine weeks after undergoing a total nephroureterectomy of the right kidney, he had a metastasectomy at port site. Within 14 weeks of the initial surgery, multiple recurrent tumors developed in the right retroperitoneal space. The pathological diagnosis was FH-deficient RCC. Genetic testing identified a heterozygous germline mutation of FH (c.641_642delTA), which confirmed the diagnosis of HLRCC-RCC. He received combination therapy with the immune checkpoint inhibitors (ICIs) nivolumab and ipilimumab as the first-line therapy. After 31 weeks of ICI treatment, a complete response was achieved. The disease-free condition has been prolonged for 24 months since the initial surgical treatment. This is the first case report of successful treatment of HLRCC-RCC with nivolumab plus ipilimumab. This combination immunotherapy is expected to be an effective approach to treat patients with advanced-stage HLRCC-RCC.

遗传性平滑肌瘤病和肾细胞癌 (HLRCC) 是一种罕见的常染色体显性遗传疾病，由延胡索酸水合酶基因 ( FH )的种系突变引起。具有FH突变的个体有患肾细胞癌 (RCC) 的风险。HLRCC 相关 RCC (HLRCC-RCC) 患者具有积极的临床病程，但目前尚无针对晚期 HLRCC-RCC 的标准化治疗。我们报告了一名 49 岁男性的激进 RCC 病例。在接受右肾全肾输尿管切除术 9 周后，他在端口部位进行了转移瘤切除术。在初次手术后的 14 周内，右侧腹膜后间隙出现多个复发性肿瘤。病理诊断为 FH 缺陷型 RCC。基因检测发现了一个杂合种系突变FH (c.641_642delTA)，证实了 HLRCC-RCC 的诊断。他接受了免疫检查点抑制剂 (ICIs) nivolumab 和 ipilimumab 的联合治疗作为一线治疗。经过 31 周的 ICI 治疗，取得了完全的反应。自最初的手术治疗以来，无病状态已延长了 24 个月。这是纳武单抗联合易普利姆玛成功治疗 HLRCC-RCC 的首个病例报告。这种联合免疫疗法有望成为治疗晚期 HLRCC-RCC 患者的有效方法。