clear-cell renal-cell carcinoma clear-cell renal-cell carcinoma clear-cell renal-cell carcinoma (ccrcc) is a type of renal-cell carcinoma. genetics cytogenetics alterations of chromosome 3p segments occurs in 70–90% of ccrccs inactivation of von hippel–lindau disease (vhl) gene by gene mutation and promoter hypermethylation gain of chromosome 5q loss of chromosomes 8p, 9p, and 14q molecular genetics several frequently mutated genes were discovered in ccrcc: vhl, kdm6a/utx, setd2, kdm5c/jarid1c and mll2. pbrm1 is also commonly mutated in ccrcc. histogenesis ccrcc is derived from the proximal convoluted tubule. microscopy generally, the cells have a clear cytoplasm, are surrounded by a distinct cell membrane and contain round and uniform nuclei. microscopically, ccrccs are graded by the isup/who as follows: grade 1: inconspicuous and basophilic nucleoli at magnification of 400 times grade 2: clearly visible and eosinophilic nucleoli at magnification of 400 times grade 3: clearly visible nucleoli at magnification of 100 times grade 4: extreme pleomorphism or rhabdoid and/or sarcomatoid morphology epidemiology ccrcc most commonly affects male patients in their sixties and seventies. majority of cases arise sporadically. only 2–4% of the cases presenting as part of an inherited cancer syndrome, such as von hippel–lindau disease. images clear-cell renal-cell carcinoma. macroscopy clear-cell renal-cell carcinoma. he, × 100 clear-cell renal-cell carcinoma. fuhrman grade = 1. he, × 400 grade 3: arrows point at a clearly visible nucleolus.