Case report: Response to immunotherapy and Association with FH gene in Hereditary Leiomyomatosis and Renal Cell Cancer Associated Renal Cell Carcinoma

Hereditary leiomyomatosis and renal cell cancer (HLRCC) was a rare autosomal dominant syndrome caused by germline mutation in the fumarate hydratase (FH) gene; it manifestsas cutaneous leiomyomas, uterine fibroids, and renal cell cancer (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) had aggressive clinical courses, but there was no standardized therapy for advanced HLRCC-RCC. In this study, we described an aggressive HLRCC in a 33-year-old female who exhibited a novel heterozygous germline insertion mutation in exon 8 of the FH gene (c.1126C>T; p.Q376*). The patient underwent laparoscopic resection of the right kidney, but metastases appeared within 3 months postoperatively. Histological staining of the resected tumor showed high expression levels of programmed cell death-ligand 1 (PD-L1). Therefore, the patient was treated with immunotherapy. The patient achieved partial response in immunotherapy and metastatic lesions had continued to benefit until now. A review of the literature identified 76 previously reported cases of HLRCC-related RCC in immunotherapy and 46 patients were enrolled in this study to analysis the correlation of FH gene and efficacy of immunotherapy. Our results indicated that the different mutations of FH germline gene were not affect efficacy of immunotherapy and immunotherapy could significantly improve the OS of HLRCC patients. Therefore, our study suggested that immunotherapy treatment was an effective therapeutic option for patients with HLRCC regardless of what form of FH germline mutation.