Supplementary Material for: Course of Multimodal Therapy and Genetic Profile of HLRCC with Early Recurrence During Adjuvant Therapy After Radical Nephrectomy

Introduction
Fumarate hydratase-deficient renal cell carcinoma is a rare and aggressive subtype associated with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome, characterized by germline mutations in the fumarate hydratase (FH) gene. Here, we report a case of HLRCC with early recurrence during adjuvant therapy following radical nephrectomy.
Case presentation
A 34-year-old woman with FH-deficient RCC presented with fever, right flank pain, and a large renal mass with a tumor thrombus. Open radical nephrectomy and IVC tumor thrombectomy were performed. Pathological findings and genetic analyses confirmed the diagnosis of HLRCC. Despite adjuvant pembrolizumab therapy after nephrectomy, bone metastases were detected within nine weeks. The patient was treated with stereotactic body radiotherapy (SBRT), followed by systemic therapy with nivolumab and cabozantinib. After 16 months since the recurrence, no further disease progression was observed. Genetic counseling revealed the same FH mutation in her daughter, prompting annual surveillance.
Conclusion
This case highlights the potential efficacy of combining tyrosine kinase inhibitor therapy with SBRT in managing aggressively progressive HLRCC.

引言
富马酸水合酶缺陷型肾细胞癌（fumarate hydratase-deficient renal cell carcinoma）是一类罕见且侵袭性极强的亚型，与遗传性平滑肌瘤病和肾细胞癌（HLRCC）综合征相关，其核心特征为富马酸水合酶（fumarate hydratase, FH）基因存在种系突变。本研究报告1例根治性肾切除术后辅助治疗期间早期复发的HLRCC病例。

病例报告
1例34岁女性FH缺陷型肾细胞癌患者，临床表现为发热、右侧腰痛及伴瘤栓的巨大肾肿块。遂行开放性根治性肾切除术及下腔静脉瘤栓取出术。病理检查与基因分析确诊为HLRCC。尽管术后接受了帕博利珠单抗辅助治疗，但患者在术后9周内即检出骨转移。予立体定向体部放疗（SBRT）治疗，随后予以纳武利尤单抗联合卡博替尼的系统治疗。复发后16个月随访，未观察到疾病进一步进展。遗传咨询显示其女儿携带相同的FH突变，遂启动年度监测方案。

结论
本病例提示，酪氨酸激酶抑制剂联合立体定向体部放疗在管理进展性侵袭性HLRCC中具有潜在临床疗效。