Chromophobe renal cell carcinoma: current and controversial issues

Area of Science:

• Urology
• Oncology
• Pathology

Background:

• Chromophobe renal cell carcinoma (RCC) was identified 35 years ago.
• Knowledge of RCC subtypes has evolved, with new entities discovered.
• Distinguishing chromophobe-like/oncocytic neoplasms remains challenging.

Purpose of the Study:

• To review molecular findings in chromophobe-like/oncocytic neoplasms.
• To address diagnostic challenges and open questions.
• To discuss the differential diagnosis of these tumors.

Main Methods:

• Review of recent molecular findings.
• Analysis of next-generation sequencing (NGS) and DNA methylation profiling data.
• Genomic analyses of chromophobe RCC and related entities.

Main Results:

• Chromophobe RCC is a low-grade malignancy with a low metastatic risk (5-6%).
• NGS and methylation studies support a distal tubule origin for chromophobe RCC and oncocytomas.
• TP53 and PTEN are frequently mutated in chromophobe RCC; TSC2/MTOR alterations are seen in 'unclassified' RCC.

Conclusions:

• Chromophobe RCC is a distinct, low-malignancy tumor entity.
• Molecular profiling aids in differentiating chromophobe-like neoplasms.
• Further research into 'oncocytic/chromophobe RCC, NOS' is warranted for identifying TSC1/2 mutations.