A case report of perioperative immune checkpoint inhibitor therapy achieving long-term disease control in TFEB-amplified renal cell carcinoma

TFEB-amplified renal cell carcinoma (RCC) is an exceptionally rare and aggressive molecular subtype of kidney cancer, recently recognised in the updated WHO classification. Its diagnosis is complicated by histological heterogeneity and overlapping features with other RCC variants, often requiring advanced molecular techniques such as FISH or genomic profiling for confirmation. Unlike more common RCC subtypes, TFEB-amplified RCC lacks standardised treatment protocols, and no approved targeted therapies currently exist. While surgical resection remains the cornerstone of management, systemic therapy options- such as tyrosine kinase inhibitors and immune checkpoint inhibitors- have shown variable efficacy in isolated case reports. The rarity of this entity poses significant challenges to evidence-based treatment development and precision oncology, underscoring the urgent need for collaborative research. This case report describes an asymptomatic 67-year-old patient with TFEB-amplified RCC in the right kidney who underwent robotic-assisted right partial nephrectomy and, 6 months later, on CT, was diagnosed with local recurrence with inferior vena cava invasion and involvement of lymph nodes. The patient received perioperative treatment with ipilimumab and nivolumab, achieving an excellent response with no further signs of disease recurrence for the last 29 months since systemic treatment initiation. These findings highlight the potential relevance of PD-L1 assessment in guiding immunotherapy decisions for this exceptionally rare histopathological subtype.