# TFEB-Amplified Renal Cell Carcinoma: Integrating Histopathologic and Molecular Diagnostics with Therapeutic Implications

## TL;DR

This paper describes a rare and aggressive kidney cancer subtype linked to TFEB gene amplification, highlighting its diagnostic challenges and poor treatment outcomes.

## Contribution

The paper presents a case of TFEB-amplified RCC with detailed histopathologic and molecular findings, emphasizing its aggressive nature and diagnostic difficulties.

## Key findings

- TFEB-amplified RCC shows heterogeneous morphology and distinct histological features like prominent nucleoli and perinucleolar clearing.
- Fluorescent in situ hybridization confirmed TFEB amplification in the tumor, supporting the diagnosis.
- The patient's rapid metastatic progression highlights the aggressive behavior and limited therapeutic options for this cancer subtype.

## Abstract

TFEB-amplified renal cell carcinoma (RCC) represents a newly described and rare aggressive molecular subtype of RCC that is characterized by TFEB gene amplification (6p21.1). These tumors are characterized by heterogeneous morphology (papillary, tubulocystic, and nested patterns), eosinophilic/clear cytoplasm, and prominent nucleoli with perinucleolar clearing. We present a diagnostically challenging lesion in a 72-year-old man who was found to have a 9.8 cm partially necrotic renal mass during work up for decreased renal function and hematuria. The nephrectomy specimen revealed a large tumor invading into the renal vein, renal sinus, and perinephric fat. Histology showed a heterogeneous tumor of clear or eosinophilic cells with prominent nucleoli and occasional perinucleolar clearing. Apically oriented nuclei were noted surrounding tubulocystic structures, as were several multinucleated tumor cells. Immunohistochemistry demonstrated Pan-keratin/Mel-A positivity. Notably, PAX8 was negative in the majority of the tumor and PD-L1 had a CPS of <5. Fluorescent in situ hybridization showed TFEB amplification (6-15 copies) and confirmed the diagnosis of TFEB-amplified RCC. Despite combined immunotherapy and anti-angiogenic therapy, the patient succumbed to rapid metastatic progression 5 months postoperatively, underscoring the tumor's aggressive behavior and current therapeutic limitations. This report outlines the diagnostic complexities associated with TFEB-amplified RCC and emphasizes the need for effective management strategies.