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: Updated: Jul 02, 2019
* 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

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.

References

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Kidney cancer
Histopathology