Clear-cell renal-cell carcinoma

Clear-cell renal-cell carcinoma (CCRCC) is a type of renal-cell carcinoma.

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.