Case Report: A patient with metastatic fumarate hydratase-deficient renal cell carcinoma associated with leiomyomatosis: real-world clinical insights on systemic therapy and liver-directed SBRT

Fumarate hydratase-deficient renal cell carcinoma is a rare type of renal cell carcinoma often associated with hereditary leiomyomatosis and renal cell carcinoma syndrome. These tumors tend to exhibit an aggressive behavior and metastasize at an early stage. We describe the case of a 41-year-old woman of Chinese ethnicity who presented with progressive left flank pain and macroscopic hematuria. Computed tomography (CT) scan of the abdomen showed a large renal mass occupying the entire left kidney, left renal vein and inferior vena cava (IVC) tumor thrombus extension, left renal hilar lymphadenopathy, and indeterminate iliac bony and multiple large uterine fibroids. The patient underwent radical nephrectomy, caval thrombectomy and IVC reconstruction, total abdominal hysterectomy, and bilateral salpingo-oophorectomies. Histopathological examination revealed metastatic fumarate hydratase-deficient renal cell carcinoma associated with uterine leiomyomatosis with R1 resection margin at IVC. Owing to the lack of uniformly agreed guidelines for the management of this tumor, close surgical surveillance was advised. The patient subsequently developed postoperative liver metastases and sought self-funded medical care abroad. She subsequently received bevacizumab and erlotinib and achieved a favorable response. However, the patient experienced renal impairment with proteinuria following treatment, and the next cycle of systemic therapy was delayed. During this pause, we proceeded with stereotactic body radiation therapy (SBRT) to the remaining solitary liver metastasis. This case illustrates the practical challenges faced in treating fumarate hydratase-deficient renal cell carcinoma, including the lack of established systemic treatment guidelines and management of treatment-related adverse events. It highlights the value of integrating radiotherapy during interruptions in systemic therapy and the importance of multidisciplinary collaboration in this rare tumor.