Fumarate hydratase-deficient renal cell carcinoma with sarcomatoid features: a case report

Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare and highly aggressive form of renal cell carcinoma (RCC), with only a few hundred cases reported worldwide. Sarcomatoid renal cell carcinoma (SRCC) is a distinctive histologic variant of RCC, accounting for approximately 1.0-1.5% of renal parenchymal tumors. To date, no standardized treatment guidelines have been established for RCC characterized by the concurrent presence of FH deficiency and sarcomatoid features.

We report a case of sarcomatoid RCC with multiple bone metastases, presenting clinically with persistent lower back pain. Genetic testing revealed a germline mutation in the FH gene. After 6 months of combined treatment with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs), the activity of the bone metastatic lesions was substantially suppressed, and the primary renal tumor was managed with cryoablation and renal artery embolization. No local or systemic recurrence has been observed, and the patient has maintained a progression-free survival (PFS) for nearly 1 year.

RCC with both FH gene loss and sarcomatoid differentiation is an exceedingly rare entity. Genetic testing and immunohistochemistry are critical for accurate diagnosis. Immunotherapy and targeted therapies may serve as potential translational treatment strategies, offering an opportunity for effective management of the primary tumor in conjunction with radiotherapy.