Understanding pathologic variants of renal cell carcinoma: distilling therapeutic opportunities from biologic complexity

Context: Once believed to represent a uniform malignant phenotype, renal cell carcinoma (RCC) is now viewed as a diverse group of cancers that arise from the nephron.

Objective: To review the pathologic characteristics, clinical behavior, molecular biology, and systemic therapy options of recognized RCC histologic subtypes.

Evidence acquisition: A systematic review of English-language articles was performed using the Medline and Web of Science databases. Manuscripts were selected with consensus of the coauthors and evaluated using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria.

Evidence synthesis: The major findings of the evaluated manuscripts are discussed with an emphasis on the description of the pathologic features, clinical behavior, prognosis, and therapeutic strategies.

Conclusions: Classification schemes for kidney cancer have undergone dramatic changes over the past two decades. Improvements in these classification schemes are important, as pathologic variants differ not only in disease biology, but also in clinical behavior, prognosis, and response to systemic therapy. In the era of genomic medicine, further refinements in characterization of RCC subtypes will be critical to the progress of this burgeoning clinical space.

Patient summary: Kidney cancer can be subdivided into related but different cancers that arise from the kidney's tubules. In this article we review current classifications for kidney cancer, discuss their characteristics, and provide an overview of each subtype's clinical behavior and treatment. We stress that each subtype harbors unique biology and thus responds differently to available treatment strategies.