Pembrolizumab plus Lenvatinib for Postoperative Recurrent TFEB-Amplified Renal Cell Carcinoma: A Case Report

Transcription factor EB (TFEB)-amplified renal cell carcinoma (RCC) is a molecularly defined subtype, newly recognized in the 2022 World Health Organization classification. Diagnosis is challenging because conventional morphologic and immunohistochemical findings are often insufficient, and confirmation typically requires fluorescence in situ hybridization (FISH) or RNA sequencing. This entity is extremely rare and has been associated with an unfavorable prognosis. No standard systemic therapy has been established.

A 67-year-old man presented with gross hematuria and was diagnosed with left RCC with a renal vein tumor thrombus (cT3aN0M0). He underwent radical nephrectomy. Histopathology showed proliferation of atypical cells with pale eosinophilic or clear cytoplasm, while immunohistochemical findings were inconclusive. Partial positivity for Melan-A prompted further evaluation. FISH analysis confirmed TFEB amplification, establishing the diagnosis of TFEB-amplified RCC. No recurrence was detected 3 months postoperatively; however, intra-abdominal recurrence developed at 6 months. Given the non-clear cell histology and poor-risk classification according to the International Metastatic Renal Cell Carcinoma Database Consortium criteria, pembrolizumab plus lenvatinib was initiated. Comprehensive genomic profiling revealed a high tumor mutational burden and amplification of vascular endothelial growth factor A (VEGFA) and other genes located in the 6p21 region, supporting the molecular diagnosis. Partial response was achieved 2 months posttreatment, with a complete response confirmed 1 year later. The patient remains on combination therapy with pembrolizumab and lenvatinib, with dose adjustment of lenvatinib.

Pembrolizumab plus lenvatinib demonstrated clinical efficacy in postoperative recurrent TFEB-amplified RCC. Combination therapy incorporating immune checkpoint inhibition and VEGF-targeted treatment may represent a therapeutic option for this entity.