Genotype Phenotype Correlation of Renal Tumors in the Cancer Genome Atlas Database

Abstract

Morphological features are critical in evaluation of renal tumors and directing molecular workup. The objective of this study was to review histomorphology of renal tumors with molecular alterations of known subtypes. Renal tumors in The Cancer Genome Atlas were reviewed to identify tumors with defining molecular alterations. Single representative digital slides and pathology reports were reviewed and morphologic features recorded. Sixty tumors were identified with molecular alterations in genes characteristic of defined renal cell carcinoma (RCC) subtypes. Findings included the presence of both low- and high-grade histology in TFE3 rearranged RCCs, TFEB amplified RCCs, succinate dehydrogenase (SDH) mutated RCCs and RCCs with mutations in mismatch repair genes. Three ELOC mutated RCCs were identified, one of which demonstrated infiltrative features. Pseudostratification of nuclei in fumarate hydratase mutated RCCs and nuclear grooves in SDH mutated RCCs were intriguing findings not previously reported. Mucinous features were noted in NF2, KRAS, and SDH mutated and ALK rearranged tumors. Significant morphologic overlap was noted across most categories with limited clues for subclassification. Whereas the number of diagnostic entities for kidney tumors continues to increase, many of these have overlapping features, highlighting the significant role molecular characterization currently plays and will continue to play in the future.