Patient Case 2: Chromophobe

A 72-year-old male patient with a history of smoking and chronic obstructive pulmonary disease presented with newly diagnosed metastatic disease. Imaging revealed a large left-sided renal mass along with pulmonary nodules suspicious for metastases. Biopsy confirmed chromophobe renal cell carcinoma (RCC). Laboratory workup showed abnormalities including elevated platelets and decreased hemoglobin, contributing to a poor-risk classification based on prognostic criteria. The patient’s clinical presentation and diagnosis posed challenges due to the aggressive nature of metastatic chromophobe RCC, a subtype known to be less common and less responsive to traditional therapies compared to clear cell RCC.

When considering diagnostic and therapeutic approaches, additional testing such as next-generation sequencing and germline genetic testing was discussed, particularly to explore underlying molecular pathways that might inform treatment. Emerging evidence suggests dysregulation in the PI3K pathway may play a role in advanced chromophobe RCC, although the impact on therapy response remains unclear. Imaging strategies may include PET scans to better detect metastatic spread. Histologic review is critical to identify any sarcomatoid features, which could indicate a more aggressive tumor behavior and potentially different therapeutic responsiveness. Due to the rarity of this subtype and limited clinical trial data, decisions on systemic therapy remain nuanced.

Treatment options debated included VEGF and mTOR inhibitor combinations, immune checkpoint inhibitor–based regimens, and targeted therapies. Retrospective data suggest VEGF plus mTOR inhibitors may offer improved response rates and progression-free survival in chromophobe RCC compared to other therapies. While checkpoint inhibitor combinations have shown some activity, the evidence is less consistent. Clinical trials specifically for chromophobe RCC are lacking, highlighting the urgent need for well-designed studies to define optimal management. In the meantime, personalized treatment decisions must balance potential efficacy with quality-of-life considerations and patient preferences.