Unlike in clear cell renal cell carcinoma, KRAS is not mutated in multilocular cystic clear cell renal cell neoplasm of low potential

The recent International Society Urological Pathology (ISUP) Vancouver classification of renal neoplasia distinguishes between clear cell renal cell carcinoma (CCRCC) and multilocular cystic clear cell renal cell neoplasm of low malignant potential (mcCCRCNLMP). Current data supports the latter being a low aggressive neoplasm which does not recur or metastasize after definitive surgical treatment. Therefore, differentiating mcCCRCNLMP from low-grade CCRCC with cystic changes is important for patient management. The role of the pathologist is crucial in distinguishing between both entities. Since these tumors have overlapping molecular features, including 3p deletion and VHL mutations, it would be potentially clinically relevant to identify other molecular differences which might help to differentiate between these entities. We studied six different codons of KRAS and six codons of NRAS in mcCCRCNLMP and CCRCC of low grade and stage. All cases of CCRCC had a mutation in one of the studied KRAS codons. In contrast, no mutations were found in mcCCRCNLMP. We provide preliminary data to support that CCRCC and mcCCRCNLMP, in spite of their histologic similarity, show a different pattern of KRAS gene mutation, which is consistent with the observed differences in disease progression between these tumors.