Biomedical
Case report: response to immunotherapy and association with the fh gene in hereditary leiomyomatosis and renal cell cancer-associated renal cell cancer
Peer Reviewed
Abstract
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.
Key Questions
What is the significance of identifying multiple hereditary cancer predisposition syndromes in a single patient?
Recognizing multiple hereditary cancer syndromes in a patient is crucial as it can influence cancer risk assessment, screening protocols, and personalized management strategies, ensuring comprehensive care.
How did the patient's genetic findings impact her clinical management?
The discovery of a likely pathogenic CHEK2 variant, in addition to her known MLH1 mutation, led to adjustments in her cancer screening and prevention strategies, tailored to address the risks associated with both genetic mutations.
Why is comprehensive genetic testing important even after identifying a known familial variant?
Comprehensive genetic testing can uncover additional pathogenic variants that may not be explained by a single familial mutation, providing a more complete understanding of a patient's cancer risk and informing more effective management plans.
What are the implications of this case for current genetic testing guidelines?
This case suggests that current guidelines may need to be updated to recommend broader genetic testing for individuals with personal or family histories suggestive of multiple hereditary cancer syndromes, even if a known familial variant has been identified.
