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综合征，由富马酸水合酶 (FH) 基因种系突变引起，表现为皮肤平滑肌瘤、子宫肌瘤和肾细胞癌 (RCC)。 HLRCC 相关 RCC (HLRCC-RCC) 患者具有侵袭性临床病程，但晚期 HLRCC-RCC 尚无标准化治疗方法。在这项研究中，我们描述了一名 33 岁女性的侵袭性 HLRCC 病例，该女性在 FH 基因的外显子 8 中表现出新型杂合种系插入突变（c.1126 C > T；p.Q376*）。患者接受腹腔镜右肾切除术，但术后3个月内出现转移。切除肿瘤的组织学染色显示程序性细胞死亡配体 1 (PD-L1) 的高表达水平。因此，该患者接受了免疫治疗。患者对免疫治疗取得部分缓解，转移病灶的治疗持续改善。彻底的文献回顾查明了 76 例接受过免疫治疗的 HLRCC-RCC 历史病例。从这个池中，选择了 46 名患者进行这项研究，以仔细检查 FH 基因突变与免疫治疗有效性之间的关联。我们的结果表明，免疫治疗可以显着提高 HLRCC-RCC 患者的总生存期 (OS)。然而，没有观察到FH种系基因的不同突变对免疫疗法的疗效的影响。因此，我们的研究表明，无论 FH 种系突变类型如何，免疫疗法都是 HLRCC 患者的有效治疗选择。© 2024。作者。

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant syndrome caused by a germline mutation in the fumarate hydratase (FH) gene that manifests with cutaneous leiomyomas, uterine fibroids, and renal cell cancer (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is no standardized therapy for advanced HLRCC-RCC. In this study, we described a case of aggressive HLRCC in a 33-year-old female who exhibited a novel heterozygous germline insertion mutation in exon 8 of the FH gene (c.1126 C > T; p.Q376*). The patient underwent laparoscopic resection of the right kidney, but metastases appeared within 3 months after surgery. Histological staining of the resected tumor revealed high expression levels of programmed cell death-ligand 1 (PD-L1). Therefore, the patient was treated with immunotherapy. The patient achieved a partial response to immunotherapy, and the treatment of metastatic lesions has continued to improve. A thorough literature review pinpointed 76 historical cases of HLRCC-RCC that had undergone immunotherapy. From this pool, 46 patients were selected for this study to scrutinize the association between mutations in the FH gene and the effectiveness of immunotherapy. Our results indicate that immunotherapy could significantly improve the overall survival (OS) of patients with HLRCC-RCC. However, no influence of different mutations in the FH germline gene on the therapeutic efficacy of immunotherapy was observed. Therefore, our study suggested that immunotherapy was an effective therapeutic option for patients with HLRCC regardless of the type of FH germline mutation.© 2024. The Author(s).