Immunohistochemical Diagnosis of Renal Neoplasms

Context—Histologic diagnosis of renal neoplasm is usually straightforward by routine light microscopy. However, immunomarkers may be essential in several contexts, including differentiating renal from nonrenal neoplasms, subtyping of renal cell carcinoma (RCC), and diagnosing rare types of renal neoplasms or metastatic RCC in small biopsy specimens. Objective—To provide a comprehensive review of the diagnostic utility of immunomarkers for renal neoplasms. Design—This review is based on published literature and personal experience. Conclusions—The following markers may have diagnostic utility in various diagnostic contexts: cytokeratins, vimentin, α-methylacyl coenzyme A racemase, carbonic anhydrase IX, PAX2, PAX8, RCC marker, CD10, E-cadherin, kidney-specific cadherin, parvalbumin, claudin-7, claudin-8, S100A1, CD82, CD117, TFE3, thrombomodulin, uroplakin III, p63, and S100P. Cytokeratins are uniformly expressed by RCC, albeit in a somewhat limited amount in some subtypes, requiring broad-spectrum anti-CK antibodies, including both low– and high–molecular-weight cytokeratins. PAX2 and PAX8 are sensitive and relatively specific markers for renal neoplasm, regardless of subtype. CD10 and RCC marker are sensitive to renal cell neoplasms derived from proximal tubules, including clear cell and papillary RCCs. Kidney-specific cadherin, parvalbumin, claudin-7, and claudin-8 are sensitive markers for renal neoplasms from distal portions of the nephron, including chromophobe RCC and oncocytoma. CK7 and α-methylacyl coenzyme A racemase are sensitive markers for papillary RCC; TFE3 expression is essential in confirming the diagnosis of Xp11 translocation RCC. The potentially difficult differential diagnosis between chromophobe RCC and oncocytoma may be facilitated by S100A1 and CD82. Thrombomodulin, uroplakin III, p63, and S100P are useful markers for urothelial carcinoma. Together with high–molecular-weight cytokeratins, PAX2, and PAX8, they can help differentiate renal pelvic urothelial carcinoma from collecting duct RCC. A sensitive marker for sarcomatoid RCC is still not available. Immunomarkers are most often used for diagnosing metastatic RCC. Compared with primary RCC, expression of the above-mentioned markers is often less frequent and less diffuse in the metastatic setting. Recognizing the variable sensitivity and specificity of these markers, it is important to include at least CD10, RCC marker, PAX2, and PAX8 in the diagnostic panel.