Category:Kidney

Contributors

Yajuan J. Liu PhD, FACMG

General section on renal cell tumors

Renal cell tumors comprise a heterogeneous group of tumors arising from the nephron, with diverse histological morphology, genetic alterations, and clinical behavior. The 2016 WHO classification of renal cell tumors (listed below) is primarily based on cytoplasmic features, architectural features, anatomic location of tumors, correlation with a specific renal disease background, and molecular alterations that are pathognomonic for RCC subtypes or familial predisposition syndromes.

Renal cell tumors:

1. Clear cell renal cell carcinoma (~65%)
2. Multilocular cystic renal neoplasm of low malignant potential
3. Papillary renal cell carcinoma (~20%)
   1. Type 1
   2. Type 2
4. Hereditary leiomyomatosis and renal cell carcinoma (RCC) syndrome–associated RCC
5. Chromophobe renal cell carcinoma (~5%)
6. Collecting duct carcinoma
7. Renal medullary carcinoma
8. MiT family translocation carcinomas
9. Succinate dehydrogenase [SDH]–deficient renal carcinomas
10. Mucinous tubular and spindle cell carcinoma
11. Tubulocystic renal cell carcinoma
12. Acquired cystic disease–associated renal cell carcinoma
13. Clear cell papillary renal cell carcinoma
14. Renal cell carcinoma, unclassified
15. Papillary adenoma
16. Renal Oncocytoma (~5%)

Recent studies of The Cancer Genome Atlas (TCGA) on three major histologically defined types of RCC—clear cell, papillary, and chromophobe – showed that molecular subtypes exist within each major RCC type, and these subtypes have distinct driver mutations, unique dysregulated molecular pathways, varying clinical course, different responses to therapy, and patient survival. In addition, Specific molecular aberrations could be identified in more than one RCC type. Widespread molecular changes associated with TFE3 gene fusion or chromatin modifier genes were present within a specific subtype and spanned multiple subtypes as shown, for example, that these alterations were found in a subset of both clear cell and papillary RCC. There were differences in patient survival and in alteration of specific pathways, including hypoxia, metabolism, MAP kinase, NRF2-ARE, Hippo, immune checkpoint, and PI3K/AKT/mTOR. Presumed actionable alterations include PI3K and immune checkpoint pathways. Therefore, therapeutic strategies could be tailored to each RCC disease subset, based on their molecular subtypes.