Molecular Pathology of Kidney Tumors

Abstract

Renal neoplasms span a broad spectrum with an array of morphologic and molecular genetic alterations. Molecular characterization has led to the recognition of new tumor entities and a better understanding of already established entities. Often, morphology and immunohistochemistry can be used as surrogates to diagnose distinct renal tumor types without full molecular evaluation; however, judicious application of molecular techniques may be helpful in specific contexts. Key molecular genetic features in the most common renal neoplasms include frequent alterations of chromosome 3p in clear cell renal cell carcinoma (RCC), gains of chromosomes 7 and 17 in papillary RCC, multiple complex losses in chromophobe RCC, and a normal karyotype or loss of chromosome 1 in oncocytoma. In recent years, the application of molecular techniques has led to increased discrimination of morphologically similar entities and new diagnostic categories have been established based on molecular genetic findings, including KRAS mutations in papillary renal neoplasm with reverse polarity and alterations of the TSC1, TSC2, and mTOR genes in acquired cystic disease-associated renal cell carcinoma, renal cell carcinoma with fibromyomatous stroma, eosinophilic vacuolated tumor, and low-grade oncocytic tumor. New gene fusions have also been recognized in renal neoplasms, such as EWSR1::PATZ1 fusion in thyroid-like follicular renal cell carcinoma and ALK fusion with multiple partner genes in other RCCs. Applications of molecular studies in selecting targeted therapy will also continue to expand.