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from Part 3.1 - Molecular pathology: carcinomas
Published online by Cambridge University Press: 05 February 2015
Renal cell carcinomas
It is estimated that in the United States in 2013, approximately 65150 people will be diagnosed with kidney cancer, and 13680 will die from this disease (1). The most common malignancy of the kidney is renal cell carcinoma (RCC), a heterogeneous disease that is divided into several subtypes based on morphological features which are correlated with distinct chromosomal and molecular signatures (2). Clear-cell renal cell carcinoma (ccRCC) is the most common form and represents 75–80% of all renal neoplasias. Papillary renal cell carcinoma is the second most common adult kidney cancer and represents 10–15% of renal neoplasms. Classification of papillary RCC into two subtypes, type 1 and type 2, is supported by histologic criteria and more recently by gene-expression and cytogenetic-profiling data (3,4). Other types of RCCs are chromophobe (4–6%), collecting-duct (1%), and those forms that are yet to be classified (2%). Although sometimes referenced historically, sarcomatoid RCC is not considered an independent entity. Sarcomatoid RCC, characterized by prominent spindle cell features, is thought to represent the high-grade end of the cytological spectrum in all of the subgroups.
Surgical removal of the neoplastic tissue is the primary therapy for patients with localized tumors (5). However, approximately 30% of patients with macroscopically complete resection of RCC have recurrence after surgery. In addition, approximately 30% of patients present with metastatic disease. Patients with recurrent or metastatic RCC have a poor overall survival as advanced cases are resistant to traditional chemotherapy, radiation, and hormonal therapy. Immunotherapy with cytokines such as interferon-α or interleukin-2 (IL-2) have resulted in response rates of approximately 15%, with a smaller percentage (5–7%) exhibiting complete remission upon treatment. However, the overall ineffectiveness of these traditional treatments in the majority of patients, coupled with the development of molecularly targeted pharmacological agents, has changed the clinical management of renal cell carcinomas. To date, six targeted agents have been approved by the Food and Drug Administration for treatment of advanced RCC: sunitinib, sorafenib, temsirolimus, everolimus, bevacizumab, and pazopanib (Figure 50.1b).
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