Exploration of Morphological Features of Clear Cell Renal Cell Carcinoma With PBRM1 , SETD2 , BAP1 , or KDM5C Mutations.

The last decade has seen great advances in genomic profiling and prognosis-associated factors of clear cell renal cell carcinoma (RCC), the most common entity in kidney cancer. Following , , , , and have been validated as the most common co-occurring gene mutations in clear cell RCC by multicenter studies. However, the morphological features of clear cell RCC with co-occurring gene mutations remain unclear. In this study, we presented 20 clear cell RCCs that underwent next-generation sequencing, of which 1 tumor was reclassified as -mutated RCC. , , , and were the most common mutations, following . Morphologically, clear cell RCC with or mutation usually displayed a low-grade pattern. Cystic changes and hyalinized stroma were often observed. The Ki67 index was <10%. These observations indicated good prognosis. However, mutated may increase the malignancy of clear cell RCC with mutation. Two clear cell RCCs with mutated and developed local or distant metastases. Clear cell RCC with mutations always had high-grade patterns, and rhabdoid differentiation was also observed, indicating that mutation was associated with poor outcomes. Papillary architecture was often a feature of mutation, which is uncommon in clear cell RCC. PDL1 was positive in only one tumor with mutation, and the positivity rate was limited to 5%. B7H3 was negative in all tumors. Morphologic findings in this small cohort may suggest why mutation does not correlate with decreased survival, whereas mutation usually predicts poor outcomes.