Pathological, Immunohistochemical and Cytogenetic Features of Papillary Renal Cell Carcinoma With Clear Cell Features

Purpose: Papillary renal cell carcinoma is characterized histologically by tumors with cells arranged in a papillary pattern. Typically the cells have a chromophilic appearance but areas may show cells with clear cytoplasm, similar to those in clear cell renal cell carcinoma. Materials and Methods: We re-reviewed the histological slides of 148 patients with papillary renal cell carcinoma who underwent nephrectomy for the presence of clear cells. Results were correlated with other pathological features, immunohistochemical expression of 22 protein markers, cytogenetic analysis and overall survival. Results: Papillary renal cell carcinoma with clear cells was identified in 57 patients (39%). Clear cells were associated with higher T classification and grade, vascular invasion and type 2 papillary renal cell carcinoma. On immunohistochemistry these tumors revealed higher expression of epithelial vascular endothelial growth factor receptor-2 than papillary renal cell carcinoma without clear cells. All papillary renal cell carcinomas with clear cells expressed alpha-methylacylcoenzyme A racemase and 76% expressed cytokeratin 7. Six of 8 tumors (75%) with chromosome 3p loss had clear cell features. The presence of clear cells was retained as an independent prognostic factor on multivariate analysis. In cases of papillary renal cell carcinoma with clear cells the loss of 3p material and absent cytokeratin 7 expression were associated with a worse outcome. Conclusions: Papillary renal cell carcinoma with clear cells is a novel entity with a unique clinical, immunohistochemical and cytogenetic phenotype. The presence of clear cells is associated with aggressive pathological characteristics and poorer prognosis.