- Chromophobe renal cell carcinoma (ChRCC) is a distinct subtype of renal cell carcinoma, first recognized as a separate entity in the 1980s and formally classified by the World Health Organization (WHO) in the 1990s. It accounts for approximately 5–7% of all renal cell carcinomas, making it relatively uncommon compared to clear cell and papillary RCC. ChRCC arises from the intercalated cells of the renal collecting ducts, and its biological behavior is generally considered more favorable than that of most other renal carcinoma subtypes.
- Histologically, chromophobe RCC is characterized by large polygonal cells with pale or eosinophilic cytoplasm, prominent cell membranes, and irregular wrinkled (“raisinoid”) nuclei. The cytoplasm often contains vesicles due to numerous cytoplasmic microvesicles that are detectable under electron microscopy. The tumors are usually well-circumscribed, sometimes encapsulated, and may demonstrate a solid, trabecular, or alveolar growth pattern. Special stains, such as Hale’s colloidal iron, are often positive, which helps distinguish ChRCC from other renal tumors.
- From a genetic and molecular standpoint, chromophobe RCC shows widespread chromosomal losses rather than point mutations, with frequent losses of chromosomes 1, 2, 6, 10, 13, 17, and 21. This pattern of multiple chromosome monosomies is characteristic and aids in differentiating ChRCC from other RCC subtypes. Unlike clear cell RCC, mutations in the VHL gene are not a hallmark of ChRCC. Instead, dysregulation of mitochondrial and metabolic pathways has been implicated in its pathogenesis, which aligns with the cell of origin in the collecting duct system.
- Clinically, patients with ChRCC often present with symptoms similar to other renal tumors: hematuria, flank pain, or an abdominal mass. However, with increasing use of imaging techniques, many cases are detected incidentally at an earlier stage. The prognosis of chromophobe RCC is generally favorable, with a lower risk of metastasis and better survival outcomes compared to clear cell RCC. Nonetheless, a small subset, particularly those with sarcomatoid differentiation or aggressive histologic features, can behave aggressively and carry a poor prognosis.
- Management of ChRCC typically follows standard approaches for renal cell carcinoma, with surgical resection—partial or radical nephrectomy—being the mainstay of treatment for localized disease. Given its relatively indolent nature, active surveillance may be considered in select cases, particularly small tumors in patients with comorbidities. Systemic therapy options for advanced or metastatic chromophobe RCC are less well-defined than for clear cell RCC, as most clinical trials have focused on the latter. Targeted therapies and immune checkpoint inhibitors are sometimes used, though ChRCC often shows lower responsiveness compared to clear cell RCC, highlighting the need for subtype-specific therapeutic research.
- In summary, chromophobe renal cell carcinoma is a unique renal tumor subtype with distinct histological, cytogenetic, and clinical characteristics. While generally associated with a better prognosis than most other RCCs, it requires careful diagnosis to distinguish it from morphologically similar entities and to identify cases with potentially aggressive features. Advances in molecular profiling may pave the way for more personalized treatment approaches, particularly for advanced disease.
