Intratumor heterogeneity in clear cell renal cell carcinoma: a review for the practicing pathologist

Intertumor heterogeneity, defined as the spectrum of morphological differences found in similar tumors in different patients, is a well-known event for pathologists. However, recent molecular studies have pointed to intratumor heterogeneity as one of the most important issues in human neoplasia in the next years. Clear cell renal cell carcinoma is an example of an intrinsically heterogeneous neoplasm, and some of the most salient advances in the knowledge of intratumor heterogeneity have been developed on it. This review intends to analyze this phenomenon in this tumor from the practicing pathologist's point of view. A careful study of the surgical specimen and an exhaustive tumor sampling are mandatory to keep relevant information. Currently accepted protocols designed for renal tumor sampling may be insufficient. As a result, a different approach to tumor sampling is advisable to ascertain that intratumor heterogeneity, if present, will be well represented in the selected material.