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 Von Hippel–Lindau disease (VHL), also known as Von Hippel–Lindau syndrome, is a rare disease, rare genetic disorder with multisystem involvement. It is characterized by visceral cysts and benign tumors with potential for subsequent malignant t ...

( VHL) gene by

gene mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis ...

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 SET domain containing 2 is an enzyme that in humans is encoded by the ''SETD2'' gene. Function SETD2 protein is a histone methyltransferase that is specific for lysine-36 of histone H3, and methylation of this residue is associated with active ...

KDM5C Lysine-specific demethylase 5C is an enzyme that in humans is encoded by the ''KDM5C'' gene. KDM5C belongs to the alpha-ketoglutarate-dependent hydroxylase superfamily. Function This gene is a member of the SMCY homolog family and encodes a p ...

/JARID1C and

MLL2 Histone-lysine N-methyltransferase 2D (KMT2D), also known as MLL4 and sometimes MLL2 in humans and Mll4 in mice, is a major mammalian histone H3 lysine 4 (H3K4) mono-methyltransferase. It is part of a family of six Set1-like H3K4 methyltransferase ...

. PBRM1 is also commonly mutated in CCRCC.

Histogenesis

CCRCC is derived from the

proximal convoluted tubule The proximal tubule is the segment of the nephron in kidneys which begins from the renal (tubular) pole of the Bowman's capsule to the beginning of loop of Henle. At this location, the glomerular parietal epithelial cells (PECs) lining bowman’s ...

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: Updated: Jul 02, 2019 * Grade 1: Inconspicuous and basophilic

nucleoli The nucleolus (; : nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis. The nucleolus also participates in the formation of signal recognition particles and plays a ro ...

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

Images

File:Renal cell carcinoma.jpg, Clear-cell renal-cell carcinoma. Macroscopy File:Clear cell renal cell carcinoma high mag.jpg, Clear-cell renal-cell carcinoma. HE, × 100 File:Renal clear cell ca (1) Nephrectomy.jpg, Clear-cell renal-cell carcinoma. Fuhrman grade = 1. HE, × 400 File:Histopathology of grade 3 clear cell renal cell carcinoma, annotated nucleolus.jpg, Grade 3: Arrows point at a clearly visible

nucleolus The nucleolus (; : nucleoli ) is the largest structure in the cell nucleus, nucleus of eukaryote, eukaryotic cell (biology), cells. It is best known as the site of ribosome biogenesis. The nucleolus also participates in the formation of signa ...

References

{{Reflist Kidney cancer Histopathology