Clear cell renal cell carcinoma

Clear-cell renal-cell carcinoma (ccRCC or CCRCC) is a type of renal-cell carcinoma. It is the most common form of kidney cancer in adults, accounting for an estimated 80% of all renal cell carcinomas.

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.^{[citation needed]}

Histogenesis

CCRCC is derived from the proximal convoluted tubule.^{[citation needed]}

Microscopy

Generally, the cells have a clear cytoplasm, are surrounded by a distinct cell membrane and contain round and uniform nuclei.^{[citation needed]}

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.
The majority of cases arise sporadically.
Only 2–4% of cases present 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.

References

↑ "Clear Cell Renal Cell Carcinoma - NCI". Cancer.gov. Mar 17, 2020. Retrieved August 3, 2026.
↑ YiFen Zhang. "What is the ISUP/WHO grading system for renal cell carcinoma (RCC)?". Medscape. Updated: Jul 02, 2019
↑ Moch, H. (2016). "WHO-ISUP-Graduierungssystem für Nierenkarzinome". Der Pathologe. 37 (4): 355–360. doi:10.1007/s00292-016-0171-y. ISSN 0172-8113.

[1] "Clear Cell Renal Cell Carcinoma - NCI". Cancer.gov. Mar 17, 2020. Retrieved August 3, 2026.

[2] YiFen Zhang. "What is the ISUP/WHO grading system for renal cell carcinoma (RCC)?". Medscape. Updated: Jul 02, 2019

[Moch2016-3] Moch, H. (2016). "WHO-ISUP-Graduierungssystem für Nierenkarzinome". Der Pathologe. 37 (4): 355–360. doi:10.1007/s00292-016-0171-y. ISSN 0172-8113.