Chinese Journal of Cancer www.cjcsysu.com

Renal cell carcinoma (RCC) is an important contributor to cancer 鄄 specific mortality worldwide. Targeted agents that inhibit key subtype 鄄 specific signaling pathways have improved survival times and have recently become part of the standard of care for this disease. Accurately diagnosing and classifying RCC on the basis of tumor histology is thus critical. RCC has been traditionally divided into clear 鄄 cell and non-clear鄄 cell categories, with papillary RCC forming the most common subtype of non-clear 鄄 cell RCC. Renal neoplasms with overlapping histologies, such as tumors with mixed clear 鄄 cell and papillary features and hybrid renal oncocytic tumors, are increasingly seen in contemporary practice and present a diagnostic challenge with important therapeutic implications. In this review, we discuss the histologic, immunohisto鄄 chemical, cytogenetic, and clinicopathologic aspects of these differential diagnoses and illustrate how the classification of RCC has evolved to integrate both the tumor爷s microscopic appearance and its molecular fingerprint. Key words Renal cell carcinoma, clear 鄄 cell renal carcinoma, papillary renal carcinoma, hybrid oncocytic tumors, immunohistochemistry, fluorescence in situ hybridization Revie